Pesticidally active fused bicyclic heteroaromatic compounds

Abstract

Compounds of formula (I), wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides.

Description

PESTICIDALLY ACTIVE FUSED BICYCLIC HETEROAROMATIC COMPOUNDS The present invention relates to pesticidally active, in particular insecticidally active quinazoline compounds, to processes for their preparation, to compositions comprising those compounds, and to their use for controlling animal pests, including arthropods and in particular insects or representatives of the order Acarina. W02017192385 describes certain heteroaryl-1,2,4-triazole and heteroaryl-tetrazole compounds for use for controlling ectoparasites in animals (such as a mammal and a non-mammal animal). There have now been found novel pesticidally active quinazoline and quinoline compounds. The present invention accordingly relates, in a first aspect, to a compound of the formula | ~NA3 R3 A2, ar ~ | TT fn EASA |] |! ! A4 _ AS R1 vl 7 R2a wherein: Ai, Az2 and As are, independently from each other, N or CRy; As and As are, independently from each other, N or CRy; R4a R4 1 AA R5 Qis Qe? or QP Ri is hydrogen, Ci-Cealkyl, C1-Cscyanoalkyl, aminocarbonylC1-Cealkyl, hydroxycarbonylC1-Cealkyl, C1- Cenitroalkyl, trimethylsilaneC1-Csalkyl, C1-Caalkoxy-C1-Csalkyl, C1—Cshaloalkyl, Cz-Cealkenyl, Cz- Cshaloalkenyl, C2-Csalkynyl, C2-Cshaloalkynyl, Ca-CacycloalkylCi-Czalkyl-, Cs-CacycloalkylC1-Caalkyl- wherein the Ca-Cscycloalkyl group is substituted with 1 or 2 halogen atoms, oxetan-3-yl-CHz-, Ci- Cealkylcarbonyl, C1-Csalkoxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, benzyl or benzyl substituted with 1 to 3 substituents independently selected from halogen, C1-Cesalkoxy and Ci- Ceghaloalkyl; Raza and Raz» are each independently selected from hydrogen, Ci-Caalkyl, C1-Cshaloalkyl, C1- Cshaloalkylsuflanyl, C- Caalkoxy, Ci- Cshaloalkoxy, halogen, NOz, SFs, CN, C(O)NHz, C(O)OH, C(S)NHz, Cs-Cacycloalkyl, Ca-Cscycloalkyl substituted with one to three substituents independently selected from Rx, Ca-Cscycloalkylcarbonyl, phenyl, phenyl substituted with one to three substituents independently selected from Rx, heteroaryl, heteroaryl substituted with one to three substituents independently selected from Rx ORe, piperidin-2-one-1-yl, piperidin-2-one-1-yl substituted with one to two substituents independently selected from Rx, pyridin-2-one-1-yl, pyridin-2-one-1-yl substituted with one to two substituents independently selected from Ry, azetidin-1-yl, azetidin-1-yl substituted with one to two substituents independently selected from Rx pyrrolidin-1-yl, pyrrolidin-1-yl substituted with one to two substituents independently selected from Rx, Cs-CecycloalkylC1-Caalkyl, Ca-CecycloalkylCi- Caalkyl substituted with one to two substituents independently selected from Rz; Ca-CecycloalkylC1- Csalkoxy, Ca-CecycloalkylC1-Caalkoxy substituted with one to two substituents independently selected from Rx, Ci-Cscyanoalkyl, C1-Cscyanoalkoxy, C1-Csalkylsulfanyl, C1-Csalkylsulfanyl substituted with one to three substituents independently selected from Rx, Ci-Caalkylsulfonyl, C1-Caalkylsulfonyl substituted with one to three substituents independently selected from Rx, C1-Csalkylsulfinyl, and Ci- Caalkylsulfinyl substituted with one to three substituents independently selected from Rx; Rs is C1-Caalkyl or C1-Cshaloalkyl; Rs is pyridine, pyrimidine, pyrazine or pyridazine; or Rs is pyridine, pyrimidine, pyrazine or pyridazine each of which, independently of each other, is substituted with one to two substituents independently selected from Ci-Caalkyl, C1-Cshaloalkyl, C1- Caalkoxy, Ca-Cacycloalkyl, halo, hydroxyl, CN, Ci-Cshaloalkoxy, C2-Cshaloalkenyloxy, Cz- Cehaloalkynyloxy, Cs-Cshalocycloalkoxy. NH2C(O)-, NHzC(S)-, (OH)N=C(NHz)- and a 5-membered heteroaryl ring optionally substituted by 1 to 3 substituents independently selected from halogen, C+- Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy and Ci-Cshaloalkoxy; Rusa is pyridine, pyrimidine, pyrazine, pyridazine; or Rusa is pyridine, pyrimidine, pyrazine or pyridazine each of which, independently of each other, is substituted with one to three substituents independently selected from C1-Caalkyl, C1-Cshaloalkyl, Cs- Caalkoxy, Ca-Cacycloalkyl, halogen, hydroxyl, cyano, and Ci-Cshaloakoxy: or Raa is Y1, Y2, Y3, and Y4 Rig, R's 7 \ Net nn wherein, R's, R's, and R's, independently of each other and independently of Y1 to Y4, are selected from hydrogen, halogen, CN, C+-Caalkyl, C1-Cshaloalkyl, Ca-Cacycloalkyl, C1-Csalkoxy, and Ci- Cshaloalkoxy; Rs is hydrogen, Ci-Caalkyl, C1-Cahaloalkyl, Ca-Cscycloalkyl, C1-Caalkoxy, Ca-CsalkoxyC(O)-, (Ci- Caalkoxy)2CH-, halogen, CN, NH2C(0), amino (i.e NHz), (C1-Csalkyl)amino, di(C+-Caalkyl)amino, hydroxy, Ca-Cshalocycloalkyl, Cs-Cacyanocycloalkyl, C2-Csalkenyl, Cz-Cshaloalkenyl, Cz-Csalkynyl, Cz Cshaloalkynyl, Ci-Cshaloalkylsulfanyl, C1-Cshaloalkylsulfinyl, C1-Cshaloalkylsulfonyl, C1- Caalkylsulfanyl, C1-Csalkylsulfinyl, C1-Csalkylsulfonyl, Ci-Caalkoxy-Ci-Caalkyl, C1-Caalkoxy-C1- Csalkoxy-C1-Caalkyl, (Ci-Caalkyl)sulfonylamino, (C-Caalkyl)sulfonyl(C1-Caalkyl)amino, (C1- Caalky)NHC(0), (C1-Csalky)2NC(0), (C1-Cacycloalky)NHC(O), (Ci-Cacycloalkyl)(C1-Caalky)NC(O), (C1-Caalkyl)C(O)(C1-Csalky)N, (C1-Csalky)C(O)NH, (C1-Csalkyl)C(O), (C1-Csalkoxy)C(O), HC(O), diphenylmethanimine, Ci-Cshaloalkoxy, phenyl, or a 5-membered heteroaromatic ring; or Rs is phenyl substituted with one to three substituents selected from C1-Caalkyl, C1-Cshaloalkyl, C1- Caalkoxy, Ca-Cacycloalkyl, halogen, CN and hydroxyl: or Rs is a 5-membered heteroaromatic ring substituted with one to three substituents selected from Cs- Caalkyl, C1-Cahaloalkyl, C1-Caalkoxy, Ca-Cacycloalkyl, halogen, CN and hydroxyl: Rss and Rss are, independently of each other, selected from hydrogen, halogen, CN, Ci-Caalkyl, Ci- Cshaloalkyl, Ca-Cacycloalkyl, C1-Caalkoxy, and C1-Cshaloalkoxy: Re is phenyl, benzyl, heteroaryl, or Ca-Cs cycloalkyl; or Res is phenyl, benzyl, heteroaryl, or Cs-Cs cycloalkyl, each of which, independent of each other, is substituted with one to three substituents independently selected from Rx; Rx is independently selected from halogen, C+-Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy, C1-Cshaloalkoxy, NO2, SFs, CN, C(O)NHz, C(S8)NH2, C1-Cshaloalkylsulfanyl, C1-Cshaloalkylsulfinyl, Ci- Cshaloalkylsulfonyl, C1-Csalkylsulfanyl, Ci-Caalkylsulfinyl and Ci-Csalkylsulfonyl; Ry is selected from hydrogen, C1-Cs alkyl, C1-Cs haloalkyl, C1-Cs alkoxy, C1-Cs haloalkoxy, halogen, CN and cyclopropyl; and Rz is selected from oxo, halogen, C1-Cs alkyl, C1-Cshaloalkyl, C1-Csalkoxy, Ci-Cshaloalkoxy and CN; or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer and N-oxide of the compound of formula I. Compounds of formula | which have at least one basic centre can form, for example, acid addition salts, for example with strong inorganic acids such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, a phosphorus acid or a hydrohalic acid, with strong organic carboxylic acids, such as Ci-Csalkanecarboxylic acids which are unsubstituted or substituted, for example by halogen, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid, or with organic sulfonic acids, such as C1-Csalkane- or arylsulfonic acids which are unsubstituted or substituted, for example by halogen, for example methane- or p-toluenesulfonic acid. Compounds of formula | which have at least one acidic group can form, for example, salts with bases, for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- or dimethylpropylamine, or a mono-, di- or trihydroxy-lower-alkylamine, for example mono-, di- or triethanolamine. In each case, the compounds of formula | according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form. N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991. The compounds of formula | according to the invention also include hydrates which may be formed during the salt formation. The term "C1-Cnalky!” as used herein refers to a saturated straight-chain or branched hydrocarbon radical attached via any of the carbon atoms having 1 to n carbon atoms, for example, any one of the radicals methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2, 2-dimethylpropyl, 1- ethylpropyl, n-hexyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2 dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, or 1-ethyl-2-methylpropyl. The term "C+-Cnhaloalkyl" as used herein refers to a straight-chain or branched saturated alkyl radical attached via any of the carbon atoms having 1 to n carbon atoms (as mentioned above), where some or all of the hydrogen atoms in these radicals may be replaced by fluorine, chlorine, bromine and / or iodine, i.e., for example, any one of chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 2- fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2- fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2,2,3,3,3- pentafluoropropyl, heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-(chloromethyl)-2-chloroethyl, 1- (bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl or nonafluorobutyl. According a term "C1-Cofluoroalkyl" would refer to a C1-Czalkyl radical which carries 1, 2, 3, 4, or 5 fluorine atoms, for example, any one of difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2- difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl or pentafluoroethyl. The term "C1-Cnalkoxy" as used herein refers to a straight-chain or branched saturated alkyl radical having 1 to n carbon atoms (as mentioned above) which is attached via an oxygen atom, i.e., for example, any one of the radicals methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1- methylpropoxy, 2-methylpropoxy or 1,1-dimethylethoxy. The term “haloC1-Cnalkoxy" as used herein refers to a C1-Cnalkoxy radical where one or more hydrogen atoms on the alkyl radical is replaced by the same or different halo atom(s) - examples include tnfluoromethoxy, 2-fiuoroethoxy, 3- fluoropropoxy, 3,3,3-trifluoropropoxy, 4-chlorobutoxy. The term “C1-Cncyanoalkyl” as used herein refers to a straight chain or branched saturated Ci-Cnalkyl radical having 1 to n carbon atoms (as mentioned above), where one of the hydrogen atoms in these radicals is be replaced by a cyano group: for example, cyanomethyl, 2-cyanoethyl, 2-cyanopropyl, 3- cyanopropyl, 1-(cyanomethyl)-2-ethyl, 1-(methyl)-2-cyanoethyl, 4-cyanobutyl, and the like. The term “Cs-Cncycloalkyl” as used herein refers to 3-n membered cycloalkyl groups such as cyclopropane, cyclobutane, cyclopentane and cyclohexane. The term “Ca-Cncycloalkylcarbonyl” as used herein refers to a 3-n membered cycloalkyl group attached to a carbonyl (C=0) group, which carbonyl group is connected to the rest of the molecule. Similarly the terms "C1-Cnalkylcarbony”, “C1-Caalkoxycarbonyl”, “phenyloxycarbonyl” and “benzyloxycarbonyl” as used herein refers to an alkyl, alkoxy, phenyloxy and benzyloxy group attached to a carbonyl (C=O) group, which carbonyl group is connected to the rest of the molecule. The term “Cs-Cacycloalkyl-C1-Czalkyl* as used herein refers to 3 or 4 membered cycloalkyl group with either a methylene or ethylene group, which methylene or ethylene group is connected to the rest of the molecule. In the instance, the Cs-Cacycloalkyl-Ci-Czalkyl- group is substituted, the substituent(s) can be on the cycloalkyl group and / or on the alkyl group. The term “Cs-CecycloalkylCi-Cshaloalkoxy” as used herein refers to a 3 to 6 membered cycloalkyl group connected to a 1 to 4 membered haloalkoxy, which haloalkoxy group is connected to the rest of the molecule. The term “aminocarbonylC+-Cnalkyl“ as used herein refers to an alkyl radical where one of the hydrogen atoms in the radical is replaced by CONH2 group. The term “hydroxycarbonylCi-Chalkyl* as used herein refers to an alkyl radical where one of the hydrogen atoms in the radical is replaced by COOH group. The term “Ci-Cnalkylsulfanyl* as used herein refers to a C1-Cnalkyl moiety linked through a sulfur atom. Similarly, the term “C1-Cnhaloalkylthio" or “C1-Cnhaloalkylsulfanyl* as used herein refers to a C1- Crhaloalkyl moiety linked through a sulfur atom. Similarly, the term "Ca-Cacycloalkylsulfanyl” refers to 3-n membered cycloalkyl moiety linked through a sulfur atom. The term “C1-Cnalkylsulfinyl* as used herein refers to a C1-Cnalkyl moiety linked through the sulfur atom of the S(=0) group. Similarly, the term “C1-Cohaloalkylsulfinyl * or “C1-Crhaloalkylsulfinyl* as used herein refers to a Ci-Cnhaloalkyl moiety linked through the sulfur atom of the S(=0) group. Similarly, the term “Cs-Cncycloalkylsulfinyl” refers to 3-n membered cycloalkyl moiety linked through the sulfur atom of the S(=0) group. The term “C1-Cnalkylsulfonyl* as used herein refers to a Ci-Cnalkyl moiety linked through the sulfur atom of the S(=0)z group. Similarly, the term “C1-Cahaloalkylsulfonyl “ or “C1-Crhaloalkylsulfonyl* as used herein refers to a Ci-Cnhaloalkyl moiety linked through the sulfur atom of the S(=0)2 group. Similarly, the term “Cs-Cncycloalkylsulfonyl” refers to 3-n membered cycloalkyl moiety linked through the sulfur atom of the S(=0)2 group The term “trimethylsilaneC1-Chalkyl” as used herein refers to an alkyl radical where one of the hydrogen atoms in the radical is replaced by a -Si(CHa)s group. The term “Cz-Cnalkenyl” as used herein refers to a straight or branched alkenyl chain having from two to n carbon atoms and one or two double bonds, for example, ethenyl, prop-1-enyl, but-2-enyl. The term “Cz-Cnhaloalkenyl” as used herein refers to a C2-Cnalkenyl moiety substituted with one or more halo atoms which may be the same or different. The term “C2-Cnalkynyl” as used herein refers to a straight or branched alkynyl chain having from two to n carbon atoms and one triple bond, for example, ethynyl, prop-2-ynyl, but-3-ynyl. The term “Cz-Cnhaloalkynyl” as used herein refers to a C2-Cnalkynyl moiety substituted with one or more halo atoms which may be the same or different. Halogen or “halo” is generally fluorine, chlorine, bromine or iodine. This also applies, correspondingly, to halogen in combination with other meanings, such as haloalkyl The term “heteroaryl” as used herein refers to a 5- or 6-membered aromatic monocyclic ring having 1 to 3 heteroatoms independently selected from N, © and S. Examples are heteroaryls J-1 to J-35 shown in Scheme A below. Preferred heteroaryl preferred is pyridyl, pyrimidyl, and pyrazolyl. Scheme A: Heteroaryl J-1 to J-35: NX NS NN NSN 0D N Z Z Z AS Ar AN J1 Jo Ja Jd J5 J6 Ng AN AN NSN NSN NT NT N7 SN CJ [2 ™ ™ On 5 2 Nn 2 Z 2 7 J8 Jo J10 J11 J12 N- N- N: N—N N—N N—N J Ly Ay J LD J-13 J-14 J-15 J-186 J17 J-18 3 =] 27\ N=\ N= N= — pu) —0 -— 5 —A0 AN J19 4-20 421 422 4-23 U4 ND DCN N =N =N A ov AO DD Ny? NN A AY NY NP J-25 J-26 J-27 J-28 J-29 J-30 $s 0: N—N S N=N — = \ 3 Cid A ON LN So A H J-31 J-32 J-33 J-34 J-35 The pyridine, pyrimidine, pyrazine and pyridazine groups (unsubstituted or substituted) for Rs and Rea are each connected via a carbon atom on the respective ring to the rest of the compound. As used herein, the term "controlling" refers to reducing the number of pests, eliminating pests and / or preventing further pest damage such that damage to a plant or to a plant derived product is reduced. The staggered line as used herein, for example, in Q® and Y-1, represent the point of connection / attachment to the rest of the compound. As used herein, the term "pest" refers to insects, and molluscs that are found in agriculture, horticulture, forestry, the storage of products of vegetable origin (such as fruit, grain and timber); and those pests associated with the damage of man-made structures. The term pest encompasses all stages in the life cycle of the pest. As used herein, the term "effective amount" refers to the amount of the compound, or a salt thereof, which, upon single or multiple applications provides the desired effect. An effective amount is readily determined by the skilled person in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered including, but not limited to: the type of plant or derived product to be applied; the pest to be controlled & its lifecycle; the particular compound applied; the type of application; and other relevant circumstances. As one of ordinary skill in the art will appreciate, compounds of formula | contain a stereogenic centre which is indicated with an asterisk in the structure below: < in the structure below: Az AZ re Rs b Ry SN A R, Aw | Rya 1* where R1, Rzs, R2b, Ra, Q, A1, Az, Aa, Ag, and As are as defined in the first aspect. The present invention contemplates both racemates and individual enantiomers. Compounds having preferred stereochemistry are set out below. t out below. Ao. a7 he % Rab 2 SN So Ry dr | Roa I'a Particularly preferred compounds of the present invention are compounds of formula I'a: where Ri, Rza, Rav, R3, Q, As, Az, As, A4, and As are as defined in the first aspect, and stereoisomers, enantiomers, tautomers and N-oxides of the compounds of formula (I'a), and agrochemically acceptable salts thereof. The term “optionally substituted” as used herein means that the group referenced is either unsubstituted or is substituted by a designated substituent, for example, “Ca-Cacycloalkyl is optionally substituted with 1 or 2 halo atoms” means Ca-Cacycloalkyl, Cs-Cscycloalkyl substituted with 1 halo atom and Cs-Cacycloalkyl substituted with 2 halo atoms. Embodiments according to the invention are provided as set out below. In an embodiment of each aspect of the invention, A. As, Az and As are, independently from each other, N or CRy, with the proviso that no more than two out of the three are N; or B. Airand As are Nand Azis CRy; or C. As, A2and As are, independently from each other, N or CH; or D. As, A2and As are, independently from each other, N or CH, with the proviso that no more than two out of the three are N: or E. Airis N, and Az and As are CH: or F. Arand A2 CH, and Asis N: or G. Arand As are N, and Az is CH: or H. Arand As are N, and Az is CH. In an embodiment of each aspect of the invention, A. Asis CRy, and Asis N: or B. Asis CRy, and Asis CH; or C. Asis CH, and Asis N; or D. Asis N, and Asis CH; or E. As and As are both CH. In an embodiment of each aspect of the invention, A. Airis N, Az and Az are CH, and As and As are both CH; or B. Airand Az are CH, Aais N, and As and As are both CH. C. Arand As are N, Azis CH, and As is CRy and As is CH: or D. Arand As are N, Azis CH, and Asis CH and As is N: or E. Arand Asare N, Azis CH, and Asis N and As is CH: or F. Arand As are N, Azis CH, and Asis N or CH and As is CH: or G. Arand As are N, Azis CH, and As is CH and Asis N or CH: or H. Aiand As are N, Azis CH, and As and As are both N: or I. Ajand As are N, Az is CH, and As and As are both CH. In an embodiment of each aspect of the invention, R1 is A. hydrogen, Ci-Csalkyl, C1-Cscyanoalkyl, aminocarbonylC1-Csalkyl, hydroxycarbonylCi-Cealkyl, C1-Cenitroalkyl, trimethylsilaneC1-Cealkyl, C1-Caalkoxy-C1-Cealkyl, C1—=Cehaloalkyl, C2- Cealkenyl, C2-Cghaloalkenyl, C2-Cealkynyl, C2-Cshaloalkynyl, Ca-CacycloalkylCi-C2alkyl-, Ca- CacycloalkylCi-Czalkyl- wherein the Ca-Cscycloalkyl group is substituted with 1 or 2 halogen atoms, oxetan-3-yl-CHz-, C1-Caalkylcarbonyl, C1-Csalkoxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, or benzyl; or B. hydrogen, Ci-Cealkyl, C1-Cscyanoalkyl, aminocarbonylC1-Csalkyl, hydroxycarbonylC1-Cealkyl, C4-Cenitroalkyl, trimethylsilaneC1-Csalkyl, C1-Caalkoxy-C1-Cealkyl, Ci—Cshaloalkyl, Cz- Csalkenyl, C2-Cshaloalkenyl, C2-Csalkynyl, C2-Cshaloalkynyl, Ca-CacycloalkylC1-Czalkyl-, benzyloxycarbonyl, or benzyl; or C. hydrogen, C1-Cealkyl, C1-Cscyanoalkyl, aminocarbonylC1-Csalkyl, hydroxycarbonylC1-Cealkyl, C1-Caalkoxy-Ci-Csalkyl, C1—=Cshaloalkyl, C2-Csalkenyl, C2-Cshaloalkenyl, C2-Csalkynyl, C2- Cehaloalkynyl, Ca-CacycloalkylC1-Czalkyl-, benzyloxycarbonyl, or benzyl; or D. hydrogen, Ci-Csalkyl, Ci-Cscyanoalkyl, C1-Caalkoxy-Ci-Csalkyl, C1—Cshaloalkyl, C2-Csalkenyl, C2-Cshaloalkenyl, C2-Csalkynyl, C2-Cshaloalkynyl, Ca-CscycloalkylCi-Czalkyl-, benzyloxycarbonyl, or benzyl; or E. hydrogen, Ci-Caalkyl, Ci-Cacyanoalkyl, C1-Caalkoxy-Ci-Caalkyl, C1—Cshaloalkyl, C2-Csalkenyl, C2-Cshaloalkenyl, C2-Caalkynyl, C2-Cshaloalkynyl, Ca-CscycloalkylCi-Czalkyl-, benzyloxycarbonyl, or benzyl; or F. hydrogen, Ci-Caalkyl, Ci-Cacyanoalkyl, C1-Caalkoxy-Ci-Caalkyl, C1—Cshaloalkyl, C2-Csalkenyl, C2-Cshaloalkenyl, C2-Caalkynyl, C2-Cshaloalkynyl, Ca-CscycloalkylCi-Czalkyl-, benzyloxycarbonyl, or benzyl; or G. hydrogen, methyl, ethyl, cyanomethyl, methoxymethyl, cyclopropyl-methyl, allyl, propargyl, benzyloxycarbonyl, or benzyl; or H. hydrogen, methyl, ethyl, allyl, propargyl or cyclopropyl-methyl; or I. hydrogen, methyl, propargyl or cyclopropyl-methyl; an embodiment of each aspect of the invention, Rza is A. hydrogen, halogen, Ci-Caalkyl, C1-Cahaloalkyl, C1-Caalkoxy, Ci-Cahaloalkoxy, CN, Ca- Cacycloalkyl, Cs-Cscycloalkylcarbonyl, phenyl, heteroaryl selected from J-1 and J-35, each of Ca-Cacycloalkyl, phenyl or heteroaryl, independent of each other, is substituted with one to three substituents Rx ORs, piperidin-2-one-1-yl, pyridin-2-one-1-yl, azetidin-1-yl optionally substituted with Rx, pyrrolidin-1-yl, Ca-CscycloalkylC1-Csalkyl substituted with one or two substituents Rz, Cs-CscycloalkylC-Caalkoxy optionally substituted with Rx, C1-Cscyanoalkyl, C1-Cscyanoalkoxy, Ci-Caalkylsulfanyl optionally substituted by one to three substituents Rx, C1-Caalkylsulfonyl optionally substituted by one to three substituents Rx, or C1-Csalkylsulfinyl optionally substituted by one to three substituents Rx, or B. hydrogen, halogen, C1-Caalkyl, C1+-Cahaloalkyl, C1-Caalkoxy, Ci-Cshaloalkoxy, CN, Ca- Cacycloalkyl, Ca-Cscycloalkylcarbonyl, phenyl, pyrazolyl, each of Ca-Cacycloalkyl, phenyl, pyrazolyl, independent of each other, is substituted with one to three substituents Rx ORs, piperidin-2-one-1-yl, pyridin-2-one-1-yl, azetidin-1-yl optionally substituted with Rx, pyrrolidin-1- yl, Ca-CecycloalkylC1-Casalkyl optionally substituted with one or two substituents Rz, Ca- CscycloalkylC1-Caalkoxy optionally substituted with Rx, C1-Cscyanoalkyl, C1-Cscyanoalkoxy, C1-Caalkylsulfanyl optionally substituted by one to three substituents Rx, C1-Casalkylsulfonyl optionally substituted by one to three substituents Rx, or C1-Csalkylsulfinyl optionally substituted by one to three substituents Rx; or hydrogen, halogen, C1-Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy, C1-Cshaloalkoxy, CN, Ca- Cacycloalkyl, Ca-Cscycloalkylcarbonyl, phenyl or pyrazolyl, each of Ca-Cscycloalkyl, phenyl, pyrazolyl, independent of each other, is substituted with one to two substituents Rx, ORs, azetidin-1-yl optionally substituted with Rx, Cs-CacycloalkylC1-Caalkyl optionally substituted with one or two substituents Rz, Ca-CecycloalkylC1-Caalkoxy optionally substituted with Ry, C1- Caalkylsulfanyl optionally substituted by one to three substituents Rx, C1-Caalkylsulfonyl optionally substituted by one to three substituents Rx, or C1-Caalkylsulfinyl optionally substituted by one to three substituents Rx; or hydrogen, halogen, C1-Csalkyl, C1-Cshaloalkyl, C1-Csalkoxy, C1-Cshaloalkoxy, CN, Cs- Cacycloalkyl, Cs-Cscycloalkyl substituted with one to two substituents Rx Ca- Cecycloalkylcarbonyl, ORs, C3-CecycloalkylC1-Csalkyl, C3-CscycloalkylC1-Csalkyl substituted with one or two substituents Rz, C1-Csalkylsulfanyl, C1-Caalkylsulfanyl substituted by one to three substituents Rx, C1-Csalkylsulfonyl, C1-Csalkylsulfonyl substituted by one to three substituents Rx, C1-Caalkylsulfinyl, or C1-Caalkylsulfinyl substituted by one to three substituents Rx or hydrogen, halogen, Ci-Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy, C1-Cshaloalkoxy, CN, Ca- Cacycloalkyl, Ca-Cacycloalkyl substituted with one to two substituents independently selected from halogen, C1-Caalkyl and Ci-Cshaloalkyl, Cs-Cacycloalkylcarbonyl, Cs-Cacycloalkylmethyl, Ca-Cacycloalkylmethyl substituted with one to two substituents independently selected from oxo, halogen, C1-Caalkyl, and Ci-Cshaloalkyl, C1-Caalkylsulfanyl substituted with one to three halogens or C1-Czalkylsulfonyl substituted with one to three halogens; or hydrogen, halogen, C1-Csalkyl, C1-Cshaloalkyl, Ci-Csalkoxy, Ci-Cshaloalkoxy, cyclopropyl, cyclopropyl substituted with one to two substituents independently selected from halogen, methyl, and trifluoromethyl, cyclopropylcarbonyl, cyclopropylmethyl substituted with one to two substituents independently selected from oxo, halogen, and trifluomethyl, or C1.Czalkylsulfanyl substituted with one to three halogens or C1.Czalkylsulfonyl substituted with one to three halogens; or hydrogen, halogen, C1-Csalkyl, C1-Cshaloalkyl, Ci-Cshaloalkylsulfanyl, Ci-Csalkoxy, Ci- Cashaloalkoxy, CN, Ca-Cecycloalkyl, Ca-Cecycloalkyl substituted with one to three substituents independently selected from C1-Caalkyl, C1-Cshaloalkyl, cyano, and halogen, cyclopropylcarbonyl, Ca-CscycloalkylCi-Caalkyl, Ca-CscycloalkylCi-Caalkyl substituted with one to five substituents independently selected from oxo, Ci-Caalkyl, C1-Cshaloalkyl, cyano, and halogen, C1-Cscyanoalkyl, C1-Caalkylsulfonyl, C1-Cshaloalkylsulfonyl, C1-Caalkylsulfinyl, Ci- Cshaloalkylsulfinyl, Ca-Cscycloalkylsulfanyl, Ca-Cecycloalkylsulfinyl, or Ca-Cecycloalkylsulfonyl; or hydrogen, halogen, C1-Caalkyl, C1-Cshaloalkyl, Ci-Cshaloalkylsulfanyl, C1-Caalkoxy, Ci- Cahaloalkoxy, CN, Ca-Cscycloalkyl, Cs-Cecycloalkyl substituted with one or two substituents independently selected from C1-Cshaloalkyl, cyano, and halogen, Cs-Cscycloalkylcarbonyl, Ca-CscycloalkylCi-Caalkyl, Ca-CacycloalkylC1-Casalkyl substituted with one to three substituents independently selected from oxo, C1-Cshaloalkyl, cyano, and halogen, Ci-Cscyanoalkyl, Ci- Caalkylsulfonyl, C1-Cshaloalkylsulfonyl, Ci-Casalkylsulfinyl, C1-Cshaloalkylsulfinyl, Ca- Cscycloalkylsulfanyl, Ca-Cscycloalkylsulfinyl, or Ca-Cscycloalkylsulfonyl; or I. hydrogen, halogen, C1-Cshaloalkyl, C1-Cshaloalkylsulfanyl, C1-Cshaloalkoxy, Cs-Cscycloalkyl, Ca-Cecycloalkyl substituted with one or two substituents independently selected from Ci- Cashaloalkyl, cyano, and halogen, Ca-Cscycloalkylcarbonyl, Ca-CecycloalkylCi-Casalkyl, Ca- CscycloalkylC1-Csalkyl substituted with one to three substituents independently selected from oxo, Ci-Cshaloalkyl, cyano, and halogen, Ci-Cscyanoalkyl, Ci-Csalkylsulfonyl, Ci- Cshaloalkylsulfonyl, C1-Csalkylsulfinyl, C1-Cshaloalkylsulfinyl, Cs-Cecycloalkylsulfanyl, Ca- Cscycloalkylsulfinyl, or Ca-Cscycloalkylsulfonyl; or J. hydrogen, halogen, Ca-Cascycloalkyl, Ca-Cscycloalkylcarbonyl, Ca-Cscycloalkyl-C1-Czalkyl optionally substituted with one to two substituents selected from oxo, halogen, Ci-Caalkyl and Ci-Cshaloalkyl, Ci-Cshaloalkyl, Ci-Cahaloalkylsulfanyl, Ci1-Cshaloalkysulfonyl, C1-Caalkoxy, C1-Cahaloalkoxy, or CN; or K. halogen, Ci-Cshaloalkyl, Ci-Cshaloalkylsulfanyl, C1-Cshaloalkysulfonyl, or C1-Cshaloalkoxy; or L. halogen, C1-Czhaloalkyl, Ci-Czhaloalkylsulfanyl, Ci-Czhaloalkysulfonyl, or Ci-Czhaloalkoxy; or M. chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl or trifluoromethylsulfonyl; or N. fluorine, chlorine, bromine, iodine, trifluoromethylsulfanyl, trifluoromethylsulfonyl or trifluoromethyl; or O. trifluoromethyl, fluorine, bromine or chlorine. an embodiment of each aspect of the invention, Rap is A. hydrogen, halogen, Ci-Caalkyl, C1-Cshaloalkyl, Ca-Cacycloalkyl, cyclopropylcarbonyl, Ca- CscycloalkylC1-Csalkyl optionally substituted with one or two substituents Rz, Ci-Caalkoxy, C1- Cshaloalkoxy, or CN, Ci-Csalkylsulfanyl optionally substituted by one to three substituents Rx, C1-Caalkylsulfonyl optionally substituted by one to three substituents Rx, or Ci-Csalkylsulfinyl optionally substituted by one to three substituents Rx; or B. hydrogen, halogen, Ca-Cacycloalkyl, cyclopropylcarbonyl, Ca-Cascycloalkyl-Ci-Coalkyl optionally substituted with one to two substituents selected from oxo, halogen, C1-Caalkyl and Ci- Cshaloalkyl, Ci-Cahaloalkyl, C1-Cahaloalkysulfanyl, C1-Cshaloalkysulfonyl, C1-Caalkoxy, Ci- Cshaloalkoxy, or CN; or C. halogen, Ci-Cshaloalkyl, C1-Cshaloalkylsulfanyl, C1-Cshaloalkysulfonyl, or C1-Cshaloalkoxy; or D. halogen, Ci-Czhaloalkyl, C1-Czhaloalkylsulfanyl, Ci-Czhaloalkysulfonyl, or C1-Czhaloalkoxy; or E. chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethylsulfonyl; or F. fluorine, chlorine, bromine, iodine, trifluoromethylsulfanyl, trifluoromethylsulfonyl or trifluoromethyl; or G. trifluoromethyl, fluorine, bromine or chlorine. In an embodiment of each aspect of the invention, Rs is A. Ci-Caalkyl or Ci-Cshaloalkyl; or B. methyl or trifluromethyl; or C. methyl. In an embodiment of each aspect of the invention, Q is A. Q% or B. Qb. In an embodiment of each aspect of the invention, Q? is A. selected from Q2-1 to Q2-16: or B. selected from Q&-1, Q&-6, Q%7, Q%10, and Q%15; or C. Q%1 orQ&15. R4 R4 N, N, 5 A AN | EF N, Ne o— F F Q-1 oo - | 4 o Co RY EF | a2 = | ass R4 R4 R4 N, N, N, ~ 2 Np Np > \ oO Lo \ [ana = I 0 | avs == | a6 Ré R4 R4 [ AN | AN | AM N N, | AN | ~~ Ly ON TN , he a ~ , oT 0 \ [ae "Ny NA [ao | a8 R4 R4 R4 | Ay int 0 | A R4 R4 N, | N, Ng aw O— O- N 0 \ "Nr | Q:10 F | Q-12 | Q-11 R4 R4 R4 F a N, a 2 N, ~ F N= dm il ° Ir ++ 4 * F } ¥ | Q*-15 | Qe13 44 R4 Aa N—? / 5" | Q*16 In an embodiment of each aspect of the invention, Q° is A. selected from Qb-1 to Q°-13; or B. Qb1. Ré4a R4a Réa [AP | AA | AP Ne J Ne Ne CON [ aot ah NA . 1 . NA cl | aa R4a Réda Ré4a AP | AA AA Ny Noor NS TF Yor Noho Ny | ans [ara | 5 | 6 R4a R4a R4a n4a Nad nad AAW | AA APN I No 7 NS Ny NS F CFy3 a CN | avs | qe7 [oe | avo R4a R4a Ré4a nea Nada naa AA AA AA | AA | Ay | A = 1 i iif Try Ny Ny NJ ~ \ Cl EN A | Q°-11 1D. = | Qb-10 1 | QP-12 R4a ~4a | AA NO 1 NS oF F | Q13 In an embodiment of each aspect of the invention, Rs is A. pyridine, or pyrimidine; wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from C1-Caalkyl, C1-Cshaloalkyl, C1- Caalkoxy, Ca-Cacycloalkyl, halo, hydroxyl, CN, Ci-Cshaloalkoxy, C2-Cshaloalkenyloxy, Ca- Cshaloalkynyloxy, Ca-Cshalocycloalkoxy, Ca-CscycloalkylCi-Cshaloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH>)-, J-13 optionally substituted by 1 to 3 substituents independently selected from halogen, C1-Caalkyl, C4-Cahaloalkyl, C1-Caalkoxy and Ci-Cahaloalkoxy, J-20 optionally substituted by 1 to 3 substituents independently selected from halogen, C1-Caalkyl, C1-Cahaloalkyl, C1-Caalkoxy and Ci-Cshaloalkoxy and 1H-tetrazol-5-yl; or B. pyridine or pyrimidine, wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from C1-Caalkyl, C1-Cshaloalkyl, C1- Caalkoxy, Ca-Cacycloalkyl, halo, hydroxyl, CN, Ci-Cshaloalkoxy, C2-Cehaloalkenyloxy, Cz- Cshaloalkynyloxy, Ca-Cshalocycloalkoxy, Cs-CecycloalkylCi-Cshaloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH.)-, J-13 optionally substituted by Ci-Cshaloalkyl, J-20 optionally substituted by Ci-Cshaloalkyl and 1H-tetrazol-5-yl; or C. pyridine, wherein the pyridine is optionally substituted with one substituent selected from Ci- Caalkyl, Ci-Cahaloalkyl, C1-Caalkoxy, Ca-Cacycloalkyl, halo, hydroxyl, CN, Ci-Cshaloalkoxy, Cz- Cshaloalkenyloxy, C2-Cehaloalkynyloxy, Ca-Cshalocycloalkoxy, Cs-CecycloalkylCi- Cshaloalkoxy, NH2C(0)-, NH2C(S)-, (OH)N=C(NHz2)-, J-13 optionally substituted by Ci- Cshaloalkyl, J-20 optionally substituted by Ci-Cshaloalkyl and 1H-tetrazol-5-yl; or D. pyrimidine; wherein the pyrimidine is optionally substituted with one substituent selected from C1-Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy, Ca-Cscycloalkyl, halo, hydroxyl, CN, Ci-Cshaloalkoxy, C2-Cshaloalkenyloxy, C2-Cshaloalkynyloxy, Ca-Cshalocycloalkoxy, Ca-CecycloalkylCi- Cé4haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NHz)-, J-13 optionally substituted by trifluoromethyl, J-20 optionally substituted by trifluoromethyl and 1H-tetrazol-5-yl; or E. pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine is optionally substituted with one substituent selected from Ci-Caalkyl, Ci- Cshaloalkyl, C1-Caalkoxy, Ca-Cacycloalkyl, F, CI, Br, CN, and C1-Cshaloalkoxy; or F. pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine is optionally substituted with one substituent selected from Ci-Caalkyl, Ca- Cacycloalkyl, F, Cl, Br, CN, and Ci-Cshaloalkoxy; or G. pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2, 2-trifluoroethoxy; H. pyridine, or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, CI, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2- difluoroethoxy and 2,2, 2-trifluoroethoxy; or |. 5-cylopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5- difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)- pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cylopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5- trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2- trifluoroethoxy)-pyrimidine, or pyrimidine; or J. 5-cylopropylpyridin-2-yl, 5-fluoropyridin-2-yl, 5-chloropyridin-2-yl, 5-bromopyridin-2-yl, 5- difluoromethoxypyridin-2-yl, 5-trifluoromethoxypyridin-2-yl, 5-cyanopyridin-2-yl, 5-(2,2- difluoroethoxy-pyridin-2-yl, 5-(2,2,2-trifluoroethoxy)-pyridin-2-yl, pyridin-2-yl, 5- cylopropylpyrimidin-2-yl, 5-fluoropyrimidin-2-yl, 5-chloropyrimidin-2-yl, 5-bromopyrimidin-2-yl, 5-difluoromethoxypyrimidin-2-yl, 5-trifluoromethoxypyrimidin-2-yl, 5-cyanopyrimidin-2-yl, 5- (2,2-difluoroethoxy)-pyrimidin-2-yl, 5-(2,2,2-trifluoroethoxy)-pyrimidin-2-yl, or pyrimidin-2-yl; or K. pyrimidin-2-yl, pyridin-2-yl, 5-bromopyrimidin-2-yl, 5-bromopyridin-2-yl, 5-cyanopyrimidin-2-yl. or 5-cyanopyridin-2-yl; or L. pyrimidin-2-yl, 5-bromopyrimidin-2-yl, 5-bromopyridin-2-yl, or 5-cyanopyridin-2-yl. an embodiment of each aspect of the invention, Raa is A. pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine, independent of each other, is optionally substituted with one substituent selected from C1-Cshaloalkyl, Ca-Cascycloalkyl, halogen, cyano, Ci-Cshaloakoxy and selected from Y-1 to Y-4: or B. pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine, independent of each other, is optionally substituted with one substituent selected from F, CI, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2- trifluoroethoxy and selected from Y-1 to Y-4; or C. pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from Ci-Cshaloalkyl, Ca-Cscycloalkyl, halogen, cyano, Ci-Cshaloakoxy and selected from Y-1 to Y-4: or D. pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2- difluoroethoxy and 2,2,2-trifluoroethoxy and selected from Y-1 to Y-4; or E. 5-cylopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5- difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)- pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cylopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5- trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2- trifluoroethoxy)-pyrimidine, pyrimidine, or 1,2,3-triazole; or F. 5-cylopropylpyridin-2-yl, 5-fluoropyridin-2-yl, 5-chloropyridin-2-yl, 5-bromopyridin-2-yl, 5- difluoromethoxypyridin-2-yl, 5-trifluoromethoxypyridin-2-yl, 5-cyanopyridin-2-yl, 5-(2,2- difluoroethoxy)-pyridin-2-yl, 5-(2,2,2-trifluoroethoxy)-pyridin-2-yl, pyridin-2-yl, 5- cylopropylpyrimidin-2-yl, 5-fluoropyrimidin-2-yl, 5-chloropyrimidin-2-yl, 5-bromopyrimidin-2-yl, 5-difluoromethoxypyrimidin-2-yl, 5-trifluoromethoxypyrimidin-2-yl, 5-cyanopyrimidin-2-yl, 5- (2,2-difluoroethoxy)-pyrimidin-2-yl, 5-(2,2,2-trifluoroethoxy)-pyrimidin-2-yl, pyrimidin-2-yl, or 1,2,3-triazol-2-yl (or Y2); or G. 1,2,3-triazol-2-yl (or Y2), pyrimidin-2-yl, or 5-cyanopyridin-2-yl. In an embodiment of each aspect of the invention, when Y-1 is selected as Rea, R'4a and R's, independently of each other, are A. hydrogen, halogen, CN, Ci-Caalkyl, C1-Cshaloalkyl, Ca-Cscycloalkyl, C1-Csalkoxy, and Ci- Cshaloalkoxy; or B. from hydrogen, F, Cl, Br, CN, methyl, CF, cyclopropyl, methoxy and difluoromethoxy; or C. both hydrogen. In an embodiment of each aspect of the invention, when Y-2 is selected as Raa, A. R's and R's, independently of each other, are selected from hydrogen, halogen, CN, Ci- Caalkyl, Ci-Cshaloalkyl, Ca-Cscycloalkyl, C1-Caalkoxy, and Ci-Cshaloalkoxy; or B. R's and R's, independently of each other, are selected from hydrogen, F, Cl, Br, CN, methyl, CFs, cyclopropyl, methoxy and difluoromethoxy; or A. R's and R's are both hydrogen; or B. R's is hydrogen and R's is cyclopropyl. In an embodiment of each aspect of the invention, when Y-3 is selected as Res, R'4a and R's, independently of each other, are A. hydrogen, halogen, CN, Ci-Caalkyl, C1-Cshaloalkyl, Ca-Cscycloalkyl, Ci-Caalkoxy, and Ci- Cshaloalkoxy; or B. hydrogen, F, Cl, Br, CN, methyl, CF, cyclopropyl, methoxy and difluoromethoxy; or C. both hydrogen. In an embodiment of each aspect of the invention, when Y-4 is selected as R'4a, A. R's, Ran, and R's are, independently of each other, selected from hydrogen, halogen, CN, Ci- Caalkyl, C1-Cshaloalkyl, C3-Cscycloalkyl, C1-Csalkoxy, and Ci-Cshaloalkoxy; or B. R's, R's, and R's are, independently of each other, selected from hydrogen, F, Cl, Br, CN, methyl, CFs, cyclopropyl, methoxy and difluoromethoxy: or C. R's, R's, and R's are all hydrogen; or D. R's and R's are hydrogen and R'ss is CN. In an embodiment of each aspect of the invention, Rs is A. hydrogen, Ci-Caalkyl, C1-Cshaloalkyl, Ca-Cacycloalkyl, C1-Caalkoxy, halogen, Ci-Caalkoxy-C1- Caalkyl, C1-Caalkoxy-C1-Caalkoxy-C1-Caalkyl, (C1-Caalkyl)C(O), (C1-Caalkoxy)C(O), HC(O), Ci- Cshaloalkoxy or a 5-membered heteroaromatic ring wherein the 5-membered heteroaromatic ring can be optionally substituted with one to three substituents selected from C1-Caalkyl, C1- Cshaloalkyl, C1-Csalkoxy, Cs-Cscycloalkyl, halogen, CN or hydroxy; or B. hydrogen, Ci-Caalkyl, Ci-Cshaloalkyl, Ca-Cscycloalkyl, C1-Caalkoxy, halogen, Ci-Caalkoxy-C1- Caalkyl, Ci-Caalkoxy-C1-Caalkoxy-Ci-Caalkyl, (C1-Caalkyl)C(O), (C1-Caalkoxy)C(QO), HC(O) or C1-Cshaloalkoxy; or C. hydrogen, Ci-Caalkyl, Ci-Cshaloalkyl, Ca-Cscycloalkyl, C1-Caalkoxy, halogen, CI, Br, Ci- Caalkoxy-C1-Caalkyl, C1-Caalkoxy-Ci-Caalkoxy-Ci-Caalkyl, (C1-Caalky)C(Q), (C1- Caalkoxy)C(Q), or Ci-Czhaloalkoxy; or D. hydrogen, C1-Caalkyl, C1-Caalkoxy, Ca-Cacycloalkyl, C1-Cshaloalkoxy, halogen, C1-Caalkoxy- C1-Caalkyl, C1-Caalkoxy-C1-Caalkoxy-C1-Caalkyl, (C1-Caalkyl)C(O), HC(O), or (Ci- Caalkoxy)C(O); or E. hydrogen, C1-Czalkyl, C1-Czalkoxy, Ca-Cacycloalkyl, Ci-Czhaloalkoxy, halogen, C1-Czalkoxy- C1-Czalkyl, C1-Czalkoxy-C1-Czalkoxy-C1-Czalkyl, (C1-C2alkyl)C(O), HC(O), or (Ci- C2alkoxy)C(O); or F. hydrogen, methyl, trifluoromethoxy, methoxy, cyclopropyl, 2,2-difluroroethoxy, 2,2,2- trifluroroethoxy, difluoromethoxy, 2,2,2-trifluroroethyl, chloro, bromo, methoxyethoxy, methylcarbonyl, or methoxycarbonyl; or G. hydrogen. In an embodiment of each aspect of the invention, Rsa is A. hydrogen, halogen, CN, Ci-Caalkyl, C1-Cshaloalkyl, Ca-Cscycloalkyl, Ci-Caalkoxy or Ci- Cshaloalkoxy; or B. hydrogen, halogen, CN, C1-Caalkyl, C1-Cshaloalkyl, Cs-Cscycloalkyl or C1-Caalkoxy; or C. hydrogen, halogen, CN, C1-Caalkyl, C1-Cshaloalkyl or C1-Csalkoxy; or D. hydrogen, halogen, CN, Ci-Caalkyl or C1-Caalkoxy; or E. hydrogen or halogen; or F. hydrogen. In an embodiment of each aspect of the invention, Rs is A. hydrogen, halogen, CN, Ci-Cshaloalkyl, Ca-Cscycloalkyl, C1-Caalkoxy, or C1-Cshaloalkoxy: or B. hydrogen, halogen or C1-Caalkoxy; or C. hydrogen. In an embodiment of each aspect of the invention, Res is A. phenyl, benzyl, heteroaryl, or Ca-Ca cycloalkyl, each of which, independent of each other, is optionally substituted with one substituent selected from Ry; or B. phenyl, benzyl, cyclopropyl or cyclopropyl substituted with one substituent selected from Rx. In an embodiment of each aspect of the invention, Rx is independently selected from A. halogen, C1-Cshaloalkyl, C1-Caalkoxy, C1-Cshaloalkoxy or CN; or B. F, Cl, Br, OCFzH, OCHs or CN. In an embodiment of each aspect of the invention, Rz is independently selected from A. oxo, halogen, Ci-Cshaloalkyl, C1-Caalkoxy, Ci-Cshaloalkoxy or CN; or B. oxo, F, Cl, Br, OCFzH, OCHs or CN. In an embodiment of each aspect of the invention, Ry is independently selected from A. hydrogen, Ci-Cs alkyl, C1-Cs haloalkyl, C1-Cs alkoxy, C1-Ca haloalkoxy, halogen, CN and cyclopropyl; or B. hydrogen, C1-Cs alkyl, C1-Ca haloalkyl, C1-Ca alkoxy, C1-Ca haloalkoxy, halogen, and cyclopropyl; or C. hydrogen, C1-Cs alkyl, C1-Ca haloalkyl, and C1-Ca alkoxy; or D. hydrogen, methyl, trifluoromethyl, and methoxy; or E. hydrogen. The present invention, accordingly, makes available a compound of formula | having the substituents R1, Rae, Rav, R3, Q, At, Az, As, As, and As as defined above in all combinations / each permutation. Accordingly, made available, for example, is a compound of formula | with A+, Az, and As being of the first aspect (i.e. A1, Az and As are, independently from each other, N or CRy; and where Ry is of embodiment D (i.e, Ry is independently selected from hydrogen, methyl, trifluoromethyl, and methoxy); As, and As being of the embodiment B (i.e. As is CRy, and As is CH where Ry is of embodiment B (i.e, Ry hydrogen, C1-Cs alkyl, C1-Cs haloalkyl, C1-Ca alkoxy, C1-Cs haloalkoxy, halogen, or cyclopropyl); Ri being embodiment B (i.e. hydrogen, C1-Csalkyl, C1-Cscyanoalkyl, aminocarbonylC1-Csalkyl, hydroxycarbonylCi-Cealkyl, C1-Cenitroalkyl, trimethylsilaneCi-Csalkyl, C1-Csalkoxy-C1-Csalkyl, C1— Cehaloalkyl, C2-Csalkenyl, C>-Cshaloalkenyl, C2-Csalkynyl, C2-Cshaloalkynyl, Cs-CacycloalkylC1- Caalkyl-, benzyloxycarbonyl, or benzyl); Rzs being an embodiment L (i.e. halogen, Ci-Czhaloalkyl, C1- C:zhaloalkylsulfanyl, Ci-Czhaloalkysulfonyl, or Ci-Czhaloalkoxy); Rzs being embodiment B (i.e. halogen, C1-Cshaloalkyl, or Ci-Cshaloalkoxy); Rs being embodiment B (i.e. hydrogen, halogen, Cs-Cacycloalkyl, cyclopropylcarbonyl, Cs-Cacycloalkyl-C1-Czalkyl optionally substituted with one to two substituents selected from oxo, halogen, Ci-Csalkyl and C-Cshaloalkyl, C1-Cshaloalkyl, C1-Cshaloalkysulfanyl, Ci- Cshaloalkysulfonyl, C1-Caalkoxy, Ci-Cshaloalkoxy, or CN); Q being embodiment A (i.e. Q is Q®, wherein Q® can be embodiment B (i.e. Q? is selected from Q®-1, Q*-6, Q*-7, Q*-10, and Q*-15; and R* is embodiment G (i.e. pyridine, or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, CI, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2, 2-trifluoroethoxy). In an embodiment, the compound of formula | is formula laa, lab or lac (with asterisk indicating a stereogenic centre), wherein Ri, Raa, Rab, and Rs, are as defined in the first aspect and Q1 corresponds to Q as defined in the first aspect, each with the corresponding embodiments as described above. NEN Re NN Rs Ry igi Re Reb i XN Ne PZ Ry | | | | Roa Roa Ra (laa) (lac) In an embodiment, compounds having preferred stereochemistry depicted in formula I'a would also be preferred for compounds of formulae laa, lab and lac. In an preferred embodiment, a compound of formula lab with the following stereochemistry is preferred: NZ NN R3 li me R2b XN a — R1 +L. | R2a I'ab where R1, Res, R2v, Rs, Qi are as defined in the first aspect, and stereoisomers, enantiomers, tautomers and N-oxides of the compounds of formula (I'ab), and agrochemically acceptable salts thereof. In an embodiment, Q1 is A. selected from Q2® to Q* and Qb@ to Qb" or B. selected from Q2@ to Q2®: or C. selected from QP2 to Qb" or D. selected from Q® Q®°, Qc Q* Q% Qe, Q Qc QP Qb° and Q: or E. selected from Q® Q®° Qc Q* Q Q® Q° and Q®: or F. selected from Q®, Q® Q¢c, Q* QP Qb° and QPF. CN Br F 7 I N No Qee EE AN Co | No I. ~N Q* | N— Q= | N= Qu Qe F — Br I 7 EN I mN N Ri | ALN NN — AN 7 N Ny Br ay NY Qf Q¥9 Qee CN Br F I I YN N=N C NX N NU [<A IAL NIN TA Qbe ng No / ! NOS NY NU Co Qe | YY qe | YM quod F v7 CN 1 N, 1H “‘w—N 1B 1 N= N NU Qf | f A N NU Qe In an embodiment of each aspect of the invention, the compound of formula | has as As, Az and As, independently from each other, N or CRy (wherein Ry is hydrogen, methyl, trifluoromethyl, and methoxy); as A« N or CH and As as CH; as Rs hydrogen, methyl, propargy! or cyclopropyl-methyl; as Rea hydrogen, halogen, C1-Csalkyl, Ci-Cshaloalkyl, C1-Csalkoxy, C1-Cshaloalkoxy, cyclopropyl, cyclopropyl substituted with one to two substituents independently selected from halogen, methyl, and trifluoromethyl, cyclopropylcarbonyl, cyclopropylmethyl substituted with one to two substituents independently selected from oxo, halogen, and trifluomethyl, or C1.Czalkylsulfanyl substituted with one to three halogens or C1.Czalkylsulfonyl substituted with one to three halogens; as Rao hydrogen, halogen, Cs-Cacycloalkyl, cyclopropylcarbonyl, Cs-Cacycloalkyl-C1-Czalkyl optionally substituted with one to two substituents selected from oxo, halogen, C1-Csalkyl and C1-Cshaloalkyl, C1-Cshaloalkyl, C1-Cshaloalkysulfanyl, C+-Cshaloalkysulfonyl, Ci-Csalkoxy, Ci-Cshaloalkoxy, or CN; as Rs methyl; and as Q selected from Q®-1 to Q°-16 and QP-1 to Q°-13, where as Rs (for Q°-1 to Q®-16) is pyridine or pyrimidine, wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from C1-Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy, Ca-Cscycloalkyl, halo, hydroxyl, CN, Ci-Cehaloalkoxy, C2-Cshaloalkenyloxy, C2-Cehaloalkynyloxy, Ca-Cshalocycloalkoxy, Ca- CecycloalkylCi-Cshaloalkoxy, NH2C(O)-, NHzC(S)-, (OH)N=C(NHz)-, J-13 optionally substituted by Ci- Cshaloalkyl, J-20 optionally substituted by C+-Cshaloalkyl and 1H-tetrazol-5-yl; and Rea (for Qb-1 to Q®- 13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from Ci-Cshaloalkyl, Ca-Cacycloalkyl, halogen, cyano, C1-Cshaloakoxy and selected from Y-1 to Y-4 (where R'sa, R'4v, and R's, independently of each other and independently of Y-1 to Y-4, are selected from hydrogen, halogen, CN, C1-Caalkyl, C1-Cshaloalkyl, Cs-Cacycloalkyl, C1- Caalkoxy, and Ci-Cshaloalkoxy). In an embodiment of each aspect of the invention, the compound of formula | is represented by formula laa, lab or lac, has as Ry hydrogen, methyl, propargyl or cyclopropyl-methyl; as Ras hydrogen, halogen, Ci-Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy, Ci-Cshaloalkoxy, cyclopropyl, cyclopropyl substituted with one to two substituents independently selected from halogen, methyl, and trifluoromethyl, cyclopropylcarbonyl, cyclopropylmethyl substituted with one to two substituents independently selected from oxo, halogen, and trifluomethyl, or C1.Czalkylsulfanyl substituted with one to three halogens or C1.Czalkylsulfonyl substituted with one to three halogens; as Ras hydrogen, halogen, Cs-Cacycloalkyl, cyclopropylcarbonyl, Cs-Cacycloalkyl-C1-Czalkyl optionally substituted with one to two substituents selected from oxo, halogen, C1-Csalkyl and C1-Cshaloalkyl, Ci-Cshaloalkyl, C1-Cshaloalkysulfanyl, C1-Cshaloalkysulfonyl, C1-Csalkoxy, Ci-Cshaloalkoxy, or CN; as Rs methyl; and as Q selected from Q°-1 to Q2-16 and Q"-1 to Q®-13, where as R« (for Q-1 to Q°-16) is pyridine or pyrimidine, wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from C1-Csalkyl, C1-Cshaloalkyl, C1-Caalkoxy, Ca-Cscycloalkyl, halo, hydroxyl, CN, Ci-Cshaloalkoxy, C2-Cshaloalkenyloxy, Cz-Cshaloalkynyloxy, Cs-Cshalocycloalkoxy, Cs- CecycloalkylCi-Cshaloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NHz)-, J-13 optionally substituted by Ci- Cshaloalkyl, J-20 optionally substituted by Ci-Cshaloalkyl and 1H-tetrazol-5-yl; and Rea (for Qb-1 to Q®- 13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from C1-Cshaloalkyl, Ca-Cacycloalkyl, halogen, cyano, C1-Cshaloakoxy and selected from Y-1 to Y-4 (where R'sa, R's, and R'sc, independently of each other and independently of Y-1 to Y-4, are selected from hydrogen, halogen, CN, C1-Caalkyl, C1-Cshaloalkyl, Cs-Cacycloalkyl, Ci- Caalkoxy, and C+-Cahaloalkoxy). In an embodiment of each aspect of the invention, the compound of formula | is represented by formula laa, lab or lac, has as Rs hydrogen, methyl, propargyl or cyclopropyl-methyl; as Rza halogen, C1-Cshaloalkyl, C1-Cshaloalkylsulfanyl, Ci-Cshaloalkysulfonyl, or C1-Cshaloalkoxy; as Rav halogen, Ci- Cshaloalkyl, C1-Cshaloalkylsulfanyl, C1-Cshaloalkysulfonyl, or C+-Cshaloalkoxy; as Rs methyl; and as Q selected from Q2-1 to @°-16 and QP-1 to Q®-13, where as Rs (for Q®-1 to Q-16) is pyridine or pyrimidine, wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from C+-Caalkyl, C1-Cshaloalkyl, C1-Csalkoxy, Cs-Cscycloalkyl, halo, hydroxyl, CN, C1-Cshaloalkoxy, C2-Cshaloalkenyloxy, Cz-Cshaloalkynyloxy, Cs-Cshalocycloalkoxy, Ca- CecycloalkylCi-Cshaloalkoxy, NH2C(O)-, NHzC(S)-, (OH)N=C(NHz)-, J-13 optionally substituted by Ci- Cshaloalkyl, J-20 optionally substituted by C+-Cshaloalkyl and 1H-tetrazol-5-yl; and Rea (for Q®-1 to Q®- 13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from C1-Cshaloalkyl, Ca-Cacycloalkyl, halogen, cyano, C1-Cshaloakoxy and selected from Y-1 to Y-4 (where R'sa, R's, and R's, independently of each other and independently of Y-1 to Y-4, are selected from hydrogen, halogen, CN, C1-Caalkyl, C1-Cshaloalkyl, Ca-Cacycloalkyl, C1- Caalkoxy, and Ci-Cahaloalkoxy). In an embodiment of each aspect of the invention, the compound of formula | is represented by formula laa, lab or lac, has as Ry hydrogen, methyl, propargyl or cyclopropyl-methyl; as Rza halogen, Ci-Cshaloalkyl, C1-Cshaloalkylsulfanyl, Ci-Cshaloalkysulfonyl, or Ci-Cshaloalkoxy; as Ra» halogen, Ci- Cshaloalkyl, Ci-Cshaloalkylsulfanyl, C1-Cshaloalkysulfonyl, or Ci-Cshaloalkoxy; as Rs methyl; and as Q selected from Q®-1 to Q®-16 and Q°-1 to Q®-13, where as Rs (for Q*-1 to Q®-16) is pyridine or pyrimidine, wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from C1-Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy, Ca-Cscycloalkyl, halo, hydroxyl, CN, Ci-Cshaloalkoxy, C2-Cshaloalkenyloxy, Cz-Cshaloalkynyloxy, Cs-Cshalocycloalkoxy, Cs- CecycloalkylC1-Cshaloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NHz)-, J-13 optionally substituted by Ci- Cshaloalkyl, J-20 optionally substituted by Ci-Cshaloalkyl and 1H-tetrazol-5-yl; and Rusa (for Q°-1 to Q®- 13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from Ci-Cshaloalkyl, Cs-Cascycloalkyl, halogen, cyano, Ci-Cshaloakoxy and selected from Y-1 to Y-4 (where R'ss, R'sp, and R’sc are each hydrogen). In an embodiment of each aspect of the invention, the compound of formula | is represented by formula laa, lab or lac, has as Ri hydrogen, methyl, propargyl or cyclopropyl-methyl; as Rza halogen, Ci-Czhaloalkyl, C1-Czhaloalkylsulfanyl, C1-Czhaloalkysulfonyl, or Ci-Czhaloalkoxy; as Ra» halogen, Ci- Czhaloalkyl, Ci-Czhaloalkylsulfanyl, C1-Czhaloalkysulfonyl, or C1-Czhaloalkoxy; as Rs methyl; and as Q selected from Q®-1 to Q°-16 and Q°-1 to Q®-13, where as Rs (for Q*-1 to Q®-16) is pyridine or pyrimidine, wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from C1-Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy, Ca-Cscycloalkyl, halo, hydroxyl, CN, C1-Cshaloalkoxy, C2-Cshaloalkenyloxy, Cz-Cshaloalkynyloxy, Ca-Cshalocycloalkoxy, Ca- CecycloalkylCi-Cshaloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NHz)-, J-13 optionally substituted by Ci- Cshaloalkyl, J-20 optionally substituted by Ci-Cshaloalkyl and 1H-tetrazol-5-yl; and Rusa (for Q°-1 to Q®- 13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from Ci-Cshaloalkyl, Cs-Cascycloalkyl, halogen, cyano, Ci-Cshaloakoxy and selected from Y-1 to Y-4 (where R'se, Rap, and R'sc are each hydrogen). In an embodiment of each aspect of the invention, the compound of formula | is represented by formula laa, lab or lac, has as Rs hydrogen, methyl, propargyl or cyclopropyl-methyl; as Rza halogen, Ci-Czhaloalkyl, C1-Czhaloalkylsulfanyl, C1-Czhaloalkysulfonyl, or Ci-Czhaloalkoxy; as Ra» halogen, Ci- Czhaloalkyl, Ci-Czhaloalkylsulfanyl, C1-Czhaloalkysulfonyl, or C1-Czhaloalkoxy; as Rs methyl; and as Q selected from Q®-1 or Q°-1, where as Rs (for Q®-1) is pyridine or pyrimidine, wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from Ci-Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy, Ca-Cacycloalkyl, halo, hydroxyl, CN, Ci-Cshaloalkoxy, Co- Cshaloalkenyloxy, Cz-Cshaloalkynyloxy, Ca-Cshalocycloalkoxy, Ca-CscycloalkylCi-Cshaloalkoxy, NH2C(0)-, NHzC(S)-, (OH)N=C(NHz)-, J-13 optionally substituted by Ci-Cshaloalkyl, J-20 optionally substituted by C1-Cshaloalkyl and 1H-tetrazol-5-yl; and Rea (for Q>-1) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from Ci- Cshaloalkyl, Ca-Cscycloalkyl, halogen, cyano, Ci-Cshaloakoxy and selected from Y-1 to Y-4 (where R'sa, R's, and R’sc are each hydrogen). In an embodiment of each aspect of the invention, the compound of formula | is represented by formula laa, lab or lac, has as Ry hydrogen, methyl, propargyl or cyclopropyl-methyl; as Rzs chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, or trifluoromethylsulfonyl; as Ra» chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethylsulfonyl; as Rs methyl; and as Q selected from Q°-1 or Q®-1, where as Rs (for Q2-1) is pyridine or pyrimidine, wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from C1-Caalkyl, C1-Cshaloalkyl, Ci- Csalkoxy, Cs-Cacycloalkyl, halo, hydroxyl, CN, Ci-Cshaloalkoxy, C2-Cshaloalkenyloxy, C2- Cshaloalkynyloxy, Cs-Cshalocycloalkoxy, Cs-CecycloalkylCi-Cshaloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NHz2)-, J-13 optionally substituted by Ci-Cshaloalkyl, J-20 optionally substituted by C1- Cshaloalkyl and 1H-tetrazol-5-yl; and Rusa (for Q®-1) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from C1-Cshaloalkyl, Cs-Cacycloalkyl, halogen, cyano, Ci-Cshaloakoxy and selected from Y-1 to Y-4 (where Rss, R'a, and R's are each hydrogen). In an embodiment of each aspect of the invention, the compound of formula | is represented by formula laa, lab or lac, has as Ri hydrogen, methyl, propargyl or cyclopropyl-methyl; as Rza chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, or trifluoromethylsulfonyl; as Rab chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethylsulfonyl; as Rs methyl; and as Q selected from Q®-1 or Q®-1, where as Rs (for Q2-1) is pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy; and Rua (for Q°-1) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2- trifluoroethoxy and selected from Y-1 to Y-4 (where R's, R'4p, and R'sc are each hydrogen). In an embodiment of each aspect of the invention, the compound of formula | is represented by formula laa, lab or lac, has R1 as hydrogen, methyl, propargy! or cyclopropyl-methyl; as Rzs chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, or trifluoromethylsulfonyl; as Rzs chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethylsulfonyl; as Ra methyl; and as Q selected from Q®-1 or Q>-1, where as Rs (for Q®-1) is 5-cylopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5- difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)-pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cylopropylpyrimidine, 5-fluoropyrimidine, 5- chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5-trifluoromethoxypyrimidine, 5- cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2-trifluoroethoxy)-pyrimidine, or pyrimidine; and Raa (for Q°-1) is 5-cylopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5- difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)-pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cylopropylpyrimidine, 5-fluoropyrimidine, 5- chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5-trifluoromethoxypyrimidine, 5- cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2-trifluoroethoxy)-pyrimidine, pyrimidine, or 1,2,3-triazole. In an embodiment of each aspect of the invention, the compound of formula | is represented by formula lab or I'ab, which has as Ri embodiment H (preferably hydrogen, methyl, propargyl or cyclopropyl-methyl); as Rza embodiment N (preferably trifluoromethyl, fluorine, chlorine, or bromine); as Rzx embodiment F (preferably fluorine, chlorine or trifluoromethyl;); as Rs methyl; and as Q1 selected from Q@ to Q®9 and Q® to QY (preferably selected from Q*, Q**, Q*, Q¥, Q™, Q** and Qf). In a second aspect, the present invention makes available a composition comprising a compound of formula | as defined in the first aspect, one or more auxiliaries and diluent, and optionally one or more other active ingredient. In a third aspect, the present invention makes available a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound as defined in the first aspect or a composition as defined in the second aspect. In a fourth aspect, the present invention makes available a method for the protection of plant propagation material from the attack by insects, acarines, nematodes or molluscs, which comprises treating the propagation material or the site, where the propagation material is planted, with an effective amount of a compound of formula | as defined in the first aspect or a composition as defined in the second aspect. In a fifth aspect, the present invention makes available a plant propagation material, such as a seed, comprising, or treated with or adhered thereto, a compound of formula | as defined in the first aspect or a composition as defined in the second aspect. The present invention in a further aspect provides a method of controlling parasites in or on an animal in need thereof comprising administering an effective amount of a compound of the first aspect. The present invention further provides a method of controlling ectoparasites on an animal in need thereof comprising administering an effective amount of a compound of formula | as defined in the first aspect. The present invention further provides a method for preventing and / or treating diseases transmitted by ectoparasites comprising administering an effective amount of a compound of formula | as defined in the first aspect, to an animal in need thereof. Compounds of formula | can be prepared by those skilled in the art following known methods. More specifically compounds of formulae I, and I'a, and intermediates therefor can be prepared as described below in the schemes and examples. Certain stereogenic centers have been left unspecified for the clarity and are not intended to limit the teaching of the schemes in any way. The process according to the invention for preparing compounds of formula | is carried out by methods known to those skilled in the art. Compounds of formula | can be made, for example, as shown in scheme 1. Scheme 1: R3 R3 + A2 AT 43 | R2b NP A2 AY Sas R3 | AP R1 3 Ha Coa R1 A4 he Me AS R2a R2a 1 m Reaction of a compound of the formula II, wherein X1 is a leaving group, such as a halogen or sulfonate, for instance chloride, with a compound of formula Ill gives a compound of the formula |, wherein A1, A2, A3, A4, A5, R1, R2a,, R2b, R3 and Q have the same meaning as given above for compounds of the formula |. The reaction can be conducted neat or in a solvent, preferably in a solvent, such as an organic solvent, for instance acetonitrile, in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C, with or without the presence of a catalyst, for instance a metal catalyst, such as a palladium complex, and with or without the addition of a base, such as an inorganic base, for instance potassium carbonate, or an organic base, such as, for example, triethylamine. Compounds of the formula Il are either known, or they can be prepared by methods known to a person skilled in the art. Scheme 2: ye re R1 R1 XIX R3 XIX Ro Al PY XIX R3 1 ~<a HN SQ 2 | Q he a Compounds of formula Ill can be made, for example, as shown in scheme 2. Treatment of a compound of the formula V, wherein X2 is a leaving group, such as a halogen or sulfonate, for instance bromide, with an amine of the formula XIX gives compounds of the formula Ill. The reaction can be conducted neat or in a solvent, preferably in a solvent, such as an organic solvent, for instance acetonitrile, in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C, with or without the addition of a base, such as an inorganic base, for instance potassium carbonate, or an organic base, such as, for example, triethylamine. Alternatively, treatment of a compound of the formula VII with an amine of the formula XIX gives compounds of the formula III. This reaction is done in the presence of a reducing agent, such as for example hydrogen, or a hydride, such as sodium borohydride, with or without a catalyst, such as a hydrogenation catalyst, for example palladium on carbon, with or without the presence of an acid, such as acetic acid, or a Lewis acid, such as zink bromide, in a solvent or without a solvent, such as, for instance, methanol. The reaction can be conducted in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C. Such methods, and the range of conditions to perform them, for the alkylation of amines and for the reductive alkylation of amines are well known to a person skilled in the art. The amines of formula XIX are either known, or they can be prepared by methods known to a person skilled in the art. Scheme 3: R3 R3 op Ixy A A2 A x27 a Al” A3 R3 oa A2 Atl” "A3 | R2b. R3 Af2a3 tse aa re REA v EAA Aq LAS R1 - Aq _ AS R1 AA AE BE 1 AA A A4 _A5 R1 fd Ad AS Ri A4 the Te ¥ ifR1=H das wv IVa Alternatively, compounds of formula | can be made, for example, as shown in scheme 3. Reaction of an amine of the formula IV with a compound of the formula V, wherein X2 is a leaving group, such as a halogen or sulfonate, for instance bromide, gives a compound of formula I, wherein A1, A2, A3, A4, AS, R1, R2a,, R2b, R3 and Q have the same meaning as given above for compounds of the formula I. The reaction can be conducted neat or in a solvent, preferably in a solvent, such as an organic solvent, for instance acetonitrile, in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C, with or without the addition of a base, such as an inorganic base, for instance potassium carbonate, or an organic base, such as, for example, triethylamine. Such methods for the alkylation of amines, and the range of conditions to perform them, are well known to a person skilled in the art. Alternatively, reaction of an amine of the formula IVa with a compound of the formula VII gives a compound of the formula | wherein R1 is H and A1, A2, A3, A4, A5, R2a,, R2b, R3 and Q have the same meaning as given above for compounds of the formula |. This reaction is done in the presence of a reducing agent, such as for example hydrogen, or a hydride, such as sodium borohydride, with or without a catalyst, such as a hydrogenation catalyst, for example palladium on carbon, with or without the presence of an acid, such as acetic acid, or a Lewis acid, such as zink bromide, in a solvent or without a solvent, such as, for instance, methanol. The reaction can be conducted in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C. Such methods for the reductive alkylation of amines, and the range of conditions to perform them, are well known to a person skilled in the art. Scheme 4: R3 R3 R3 orm on Sa VII v vi Compounds of formula V can be made, for example, as shown in scheme 4. Treatment of a compound of the formula VIII with a halogenating agent, such as chlorine or bromine or N-bromosuccinimide, for example, gives compound of the formula V, wherein the leaving group Q is a halogen, for instance chloride or bromide. This reaction is done with or without a solvent, preferably in a solvent, with or without an additive, such as a radical starter, such as, for example, benzoyl peroxide or azoisobutyronirile. The reaction can be done with or without exposure to visible light, or to UV light, and it can be conducted in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C. Altematively, a compound of the formula VII can be treated with a reducing agent, followed by reaction with a sulfonyl chloride, for instance methanesulfonyl chloride, to give a compound of the formula V, wherein the leaving group Q is a sulfonate, for instance a mesylate. This reaction can be done in a solvent, or without a solvent, in the presence of a base, such as an inorganic base, for instance potassium carbonate, or an organic base, such as an amine base, for instange trimethylamine, or without a base, and it can be conducted in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C. A suitable reducing agent could be, for example, hydrogen, or a hydride, such as sodium borohydride, with or without a catalyst, such as a hydrogenation catalyst, for example palladium on carbon, with or without the presence of an acid, such as acetic acid, or a Lewis acid, such as zink bromide, in a solvent or without a solvent, such as, for instance, methanol. The reaction can be conducted in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C. Such methods for the halogenation, the reduction of carbonyl compounds and the sulfonylation of alcohols, and the range of conditions to perform them, are well known to a person skilled in the art. The amines of formula VII and the compounds of formula VIII are either known, or they can be prepared by methods known to a person skilled in the art. Scheme 5: AT” A3 R3 R3 pr | rs X3 A2 At” “A3 R3 | reo ANA A2 AT” “A3 R3 | R2b. ol A4 AS R1 yo H A —-> A4 __AS Mgt RA il Roa R2a Ia Alternatively, compounds of formula | wherein R1 is different from H can be made, for example, as shown in scheme 5. A compound of the formula la can be reacted with a compound of the formula VI wherein X3 is a leaving group, such as a halogen or sulfonate, for instance a chloride, bromide, iodide or mesylate, to give a compound of formula |, wherein A1, A2, A3, A4, A5, R1, R2a, R2b, R3 and Q have the same meaning as given above for compounds of the formula I. This reaction can be conducted neat or in a solvent, preferably in a solvent, such as an organic solvent, for instance acetonitrile, in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C, with or without the addition of a base, such as an inorganic base, for instance potassium carbonate, or an organic base, such as, for example, triethylamine. Such methods for the alkylation of amines, and the range of conditions to perform them, are well known to a person skilled in the art. Scheme 6: R3 + arfR ne R2b. I a?2as rs | w LL I H H R3 o HN z Aq _A5 NH NH, z 2 phe R2a 1 xX Fapho R2a 1s R2a xX ON. NUS LO xu_—~ R3 > A2 R4 A1” “A3 R3 a?2as rs — Ra iE 2 | 5 7 Ar “hs R3 Ra H I NN Noo ra, JI H Xo H TT HN xu NH2 NS A2 AY hs R3 R4 7 R2b. SNA > A4__ AS Ne Fapho R2a x1 NC Ib Pho R2a Compounds of formula Ib can be made, for example, as shown in scheme 6. Reaction of a compound of the formula II, wherein X1 is a leaving group, such as a halogen or sulfonate, for instance chloride, with a compound of formula IX gives a compound of the formula X. The reaction can be conducted neat or in a solvent, preferably in a solvent, such as an organic solvent, for instance acetonitrile or N,N-dimethylformamide, in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C, with or without the presence of a catalyst, for instance a metal catalyst, such as a palladium complex, and with or without the addition of a base, such as an inorganic base, for instance potassium carbonate, or an organic base, such as, for example, triethylamine. Subsequent treatment of compound X with the known compound XIII gives a compound of the formula XI. This reaction can be conducted neat or in a solvent, preferably in a solvent, such as an organic solvent, for instance dichloromethane, in a temperature range of -100 to +300 °C, preferably between ambient temperature and 100 °C, or between ambient temperature and 50 °C, without a base or in the presence of a base, such as an inorganic base, for instance potassium carbonate, or an organic base, such as, for example, triethylamine. Further reaction of compound XI with hydrazine XII gives the compound of formula Ib, wherein A1, A2, A3, A4, A5, R2a, R2b, R3 and R4 have the same meaning as given above for compounds of the formula I. This reaction can be conducted neat or in a solvent, preferably in a solvent, such as an organic solvent, for instance 1,4-dioxane, or acetic acid, or a mixture of 1,4-dioxane and acetic acid, in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C, or between ambient temperature and 80 °C. Within this sequence of transformations, the intermediate compounds of formula X and of formula XI can be used as crude products for the subsequent step, or they can be purified, for instance by chromatography, and used in purified form for the next transformation. Scheme 7: Nite R1 Vi M1 re R1 R3 R3 ni LA IP XIX HN x oY o SN R1 NA ! Ne R3 R4 20 NJ R3 R4 NS R1 1$ XVI XVI XVII Ma A2 AF %A3 R2b. | NY ONH, A2 Al” "A3 | R2b. nu Al Apa | R2b ye JK, phe R2a Aq he R2a A4 AS R2a R1=H| Yr : IVa R2a om a R3 Re M1 XV Af Mes R3 R4 R2b OEY = ALAS R1 Ne A2 wm mo R2b A ALAS RI NS Me R2a Me AS R2a ed I XIV ic Compounds of formula Ic can be made, for example, as shown in scheme 7. Reaction of a compound of the formula XVII with an amine of the formula XIX gives compounds of the formula XVI. This reaction is done in the presence of a reducing agent, such as for example hydrogen, or a hydride, such as sodium borohydride, with or without a catalyst, such as a hydrogenation catalyst, for example palladium on carbon, with or without the presence of an acid, such as acetic acid, or a Lewis acid, such as zink bromide, in a solvent or without a solvent, such as, for instance, methanol. The reaction can be conducted in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C. Such methods, and the range of conditions to perform them, for the reductive alkylation of amines are well known to a person skilled in the art. Subsequent reaction of the intermediate of the formula XVI with a compound of the formula II gives a compound of the formula XIV. This reaction can be conducted neat or in a solvent, preferably in a solvent, such as an organic solvent, for instance acetonitrile, in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C, with or without the presence of a catalyst, for instance a metal catalyst, such as a palladium complex, and with or without the addition of a base, such as an inorganic base, for instance potassium carbonate, or an organic base, such as, for example, triethylamine. Subsequently, the intermediate of the formula XIV is reacted with a compound of the formula XV to give the compound of formula Ic, wherein A1, A2, A3, A4, A5, R2a, R2b, R1, R3 and R4 have the same meaning as given above for compounds of the formula |, and M1 in R4-M1 is a metal, such as for instance lithium, or -MgClI, or — ZnBr, or —-B(OH)2; or R4-M1 represents a boronate, such as a pinacol ester of a boronic acid, or a stannane such as R4-Sn(n-Bu)s. Such transformations are known to a person skilled in the art as Suzuki-, Kumada-, Negishi- or Stille-coupling reactions, respectively. Such reactions are carried out in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C, in the presence of a catalyst, such as a metal catalyst, for instance a palladium catalyst, and a ligand, such as for example a phosphine ligand, or an N-heterocyclic carbene (NHC) ligand, or a phosphite ligand. The reaction can be done in the presence or absence of an additional metal catalyst, such as, for example, a copper salt, for instance Cul. The reaction is done with or without a base, which can be an inorganic base, such as potassium carbonate, or sodium hydroxide, or cesium carbonate, or an organic base, such as an amine base, for instance triethyl amine. This reaction is done with or without a solvent, preferentially in a solvent. Where the reaction mixture is heated, the reaction can be conducted under microwave irradiation or with conventional heationg, such as heating the reaction vessel in an oil bath. By an alternative route, compound XVII can be reacted with a compound of the formula XV to give intermediate XVIII. This reaction is done essentially under in the same range of conditions as described for the transformation of intermediate XIV to the compound of formula Ic. Subsequently, the intermediate XVIII is reacted with amine IV to give a compound of the formula Ic, wherein R1 is hydrogen and A1, A2, A3, A4, A5, R2a, R2b, R3 and R4 have the same meaning as given above for compounds of the formula I. This reaction is done in the presence of a reducing agent, essentially under the same conditions as described above for the transformation of compound XVII to intermediate XVI. By yet another alternative route, the intermediate compound of the formula XVIII can be reacted with an amine of the formula XIX to give the intermediate of the formula Illa. This reaction is done in the presence of a reducing agent, essentially under the same conditions as described above for the transformation of compound XVII to intermediate XVI. Subsequently, the intermediate of the formula lila is reacted with a compound of the formula Il to give the compound of the formula Ic, wherein A1, A2, A3, A4, A5, R2a, R2b, R1, R3 and R4 have the same meaning as given above for compounds of the formula I. This reaction is done essentially under the same conditions as described above for the transformation of intermediate XVI to intermediate XIV. Within these different multistep sequences, the intermediate compounds of formulas XIV, XVI, XVII and lila can be used as crude products for the respective subsequent step, or they can be purified, for instance by chromatography, and used in purified form for the next transformation. Compounds of the formula XVII are known, or they can be prepared by methods known to a person skilled in the art. Compounds of the formula Id R3 R4a R1 R23 Id A2 A “A3 R3 Raa R2b | CCV TY A4 _A5 R1 N 0 Ne R2a d R5a can be prepared by the reaction of an amine of the formula Ilib R3 R4a R1 1b wherein R1, R3, R4a, R5a and R5b are as described in formula | with a compound of the formula II A2 AY “A3 R2b. | a X1 A4 __A5 A4 __A5 ~ R2a 11 wherein A1, A2, A3, A4, A5, R2a and R2b are as described in formula | and X1 is a leaving group, such as a halogen or a sulfonate, for instance chloride. The chemistry is described in more detail in Scheme 8. Scheme 8: R3 R4a R3 R4a A2 ul “A3 | R2b NP optionaly in the presence ofa base, eg. EtN, pyridine A eant d bil id R1 Nz a NP eso A2 Lo Ro AFA RS Ria > x1 Ib R2b | 1 X Ad AS i. 7 NN SN Y optionaly in the presence MAS RT N Nps R2a of a base, e.g. Et;N, pyridine Y R2a 5a I i Reaction of a compound of the formula II, wherein X1 is a leaving group, such as a halogen or sulfonate, for instance chloride, with a compound of formula Illb gives a compound of the formula Id, wherein A1, A2, A3, A4, A5, R1, R2a, R2b, R3, R4a, R5a and R5b have the same meaning as given above for compounds of the formula |. The reaction can be conducted neat or in a solvent, preferably in a solvent, such as an organic solvent, for instance acetonitrile, in a temperature range of -100 to +300 °C, preferably between ambient temperature and 200 °C, with or without the presence of a catalyst, for instance a metal catalyst, such as a palladium complex, and with or without the addition of a base, such as an inorganic base, for instance potassium carbonate, or an organic base, such as, for example, triethylamine. The formation of compounds of formula IIIb is outlined in Scheme 9. Compounds of formula llib can be prepared by treatment of compounds of formula lic, wherein Rs, Res, Rss, and Res are as described in formula |, with compounds of formula XX wherein R1 is as defined in formula |, e.g. in the presence of NaBH(OAc)s or NaBHiCN, in a suitable solvent, preferably in acetic acid at room temperature analog to W02002 / 088073, page 35. Alternatively, another reagent system for the reductive amination uses a combination of Ti(i-OiPr)s and NaBHs (see Synthesis 2003 (14), 2206). Amines of formula Illc may be obtained by biocatalyzed deracemization of amines of formula Ilid. This may be done for instance using a lipase, e.g. Candida Antarctica lipase B or Pseudomonas fluorescens lipase, eventually in immobilized form (e.g. Novozym® 435) in presence of an acyl donor, e.g. ethyl methoxyacetate or vinyl acetate, in a suitable solvent such as acetonitrile or methyl tert-butyl ether at temperatures between 20 °C to 100 °C. Such processes are described for instance in J. Org. Chem. 2007, 72, 6918-6923 or Adv. Synth. Catal. 2007, 349, 1481-1488. The expected stereochemical outcome of such enzymatic deracemization are known of those skilled in the art and are documented in the literature, for instance in J. Org. Chem. 1991, 56, 2656-2665 or J. Am. Chem. Soc. 2015, 137, 3996-4009. Scheme 9: biocatalyst e.g. lipase or protease R3 Réa R3 Ria R3 Réa Chemoenzymatic resolution Reductive amination | SN HaN > Sy | mo 1 2 sb: RI No Pee biocatalyst e.g. lipase or protease REL Q 5b I Ama SSCS piISisee J Ra ‘acylating agent e.g. ethyl methoxyacetate or vinyl acetate 8 Pe Im solvente.g ACNorTBME ~~ Mc mb id T=2010100 °C x In an alternative process, compounds of formula llc can be obtained from compounds of the formula XXII wherein Rs, Rss, Rse, and Rsp are as described in formula |, following the synthesis described in Scheme 10: Scheme 10: Zs ‘deprotection XaV oa XxXn MMe Z, = NPhth or Boc N. Nucleaphillc substitution XXII Amines of formula Ilic may be obtained from intermediates of formula XXII, wherein Rs, Rea, Rsa, and Resp are as described in formula | and Zs is NPhth or NBocz. Such intermediates can be obtained from alcohols of formula XXI by a Mitsunobu reaction, which involves treating alcohols of formula XXI with diisopropyl azodicarboxylate in the presence of a phosphine such as triphenylphosphine or tributylphosphine and of an amine such as phthalimide or bis(tert-butoxycarbonyl)amine. Mitsunobu reactions are known by those skilled in the art to proceed with inversion of the stereocenter, as described for instance in Chem. Rev. 2009, 109, 2551-2651. Amines of formula XXII can then be transformed into amines of formula llic by treatment with hydrazine if Zs = NPhth or with acid, for example trifluoroacetic acid, if Zs = NBoca. Alternatively, amines of formula llc may be obtained by reduction of azides of formula XXIII, wherein Rs, Rss, Rsa, and Rsy are as described in formula |, by treatment with triphenylphosphine and water (Staudinger reaction) or by hydrogenation for example using a palladium catalyst in the presence of hydrogen. Azides of formula XXIII may be obtained by treatment of alcohols of formula XXI, wherein Rs, Rss, Rea, and Resp are as described in formula I, with an azidation reagent such as diphenyl phosphoryl azide in a solvent such as toluene or THF in presence of a base such as DBU. Such processes are known by those skilled in the art to proceed with inversion of the stereocenter and are described in the literature for instance in Adv. Synth. Catal. 2018, 360, 2157-2165. Alcohols of formula XXI may be obtained by enantioselective reduction of ketones of formula XXIV, wherein Rs, R4a, Rsa, and Rsp are as described in formula I. Such reductions can be done using a catalyst, for instance a ruthenium or a rhodium catalyst with a chiral ligand such as RuCI[(RR)- TsDPEN](mesitylene) or RuBF[(R, R)-TSDPEN](p-cymene) in the presence of a hydrogen donor system such as for example HCOOH / EtsN or HCOzNHs. Such processes are described in the literature for instance in J. Org. Chem. 2017, 82, 5607. Alternatively, compounds of formula Illc may also be prepared as outlined in Scheme 11. Scheme 11: Eh Réa hs mo Lh Sk R3 R4a hw we > ne use 3. Ho st _— oP 0 banzoin condensation o No FT OH LS XXL SOV he HINT SR ‘deprotection ‘solvent e.g. ethanol or isopropanol ‘oxidant e.g. air or DDQ > RI Rda oP AA - Al 7 rsp RSa XXV le Amines of formula llic can be prepared by deprotection of amines of formula XXV, wherein Ra, R4a, Rsa, and Rsp are as described in formula |, for instance using an acid such as trifluoroacetic acid or hydrochloric acid. Amines of formula XXV can be obtained by condensation of diamines of formula XXVII, wherein Rss, and Rsp are as described in formula |, on diketones of formula XXVI, wherein Rs, and Rea are as described in formula I. This condensation can take place in the presence of a suitable solvent such as ethanol or isopropanol in presence of an oxidant such as air or DDQ. Diketones of formula XXVI may be formed by oxidation of hydroxyketones of formula XXVII wherein Rs, and R4a are as described in formula |. This oxidation can involve for instance SOs-pyridine in presence of DMSO and a base for instance triethylamine or alternatively sodium hypochlorite in presence of a catalyst such as TEMPO / BusNHSOQ4. Examples of such oxidations can be found in the literature, for instance in Synlett, 2014, 25, 596 or J. Am. Chem. Soc. 1990, 112, 5290-5313. Hydroxyketones of formula XXVII may be synthesized by cross-benzoin condensation between aldehydes of formula XXIX, wherein Rss is as described in formula I, and aldehydes of formula XXVIII, wherein Rs is as described in formula I. Aldehydes of formula XXVIII are commercially available in chiral form, like for instance Boc-L-alaninal (CAS 79069-50-4) or tert-butyl N-[(1S)-1-(cyclopropylmethyl)-2-oxo-ethylcarbamate (CAS 881902-36- 9). Cross-benzoin condensations are done in the usual way by employing an organocatalyst such as a triazolium salt or a thiazolium salt in the presence of a base such as potassium tert-butoxide or isopropyldiethylamine in a suitable solvent such as DCM or THF at a temperature between -20 °C and the boiling point of the solvent. Examples of catalysts for such transformations have been described in the literature for instance in J. Am. Chem. Soc. 2014, 136, 7539-7542 or in Org. Lett. 2016, 18, 4518- 4521. Scheme 12: 123 |] R2b. Ri=H YY Four 1 do optionaly in the presence rh Ra 1 “~~ ofabase, e.g. Et,N, pyridine a™%a3 1] R2b. Reductive amination 88 Raa NP ; Ad _AS Ny Ree optionaly in the presence 5 1 Rga of a base, e.g. Et,N, pyridine R2a RH A Xo7 A1T°A3 Ry | b = Z T a ine R2a Rs OOTY XXXV XXXII XXX I. 7. LAS Rint ny My AA Ree w Ry NF i " of Rsb optional in the presence Rga of a base, e.g. Et;N, pyridi XXX Po Xg7 = Cl, Br, |, OMs, OTs or OTf Stille reaction or Suzuki-Miyaura reaction ra ysiomy | raw xXx XXX a" Rs Raa 05 nM As Ri Ps R2a u Rea As shown in Scheme 12, compounds of formula Id can be altematively prepared by reaction of compounds of formula XXX (wherein Ai, Az, As, As, As, Ri, Raza, Rab, Rs, Rsa, and Rss are as defined in formula | and Xor is a leaving group like, for example, chlorine, bromine, iodine) with compounds of formula XXXI (Stille reaction) or compounds of formula XXXII (Suzuki-Miyaura reaction) in the presence of a palladium catalyst as described in detail in Scheme 7. Compounds of formula XXX can be prepared by coupling of amines of formula XXXII and compounds of formula II, wherein A+, Az, As, As, As, Ras, Rv and Xi are described in Scheme 1, under the conditions described in detail in Scheme 1. Under the same conditions, if R1 = H, compounds of formula XXX may be obtained directly from compounds of formula XXXIV. Compounds of formula XXXIIl can be prepared by treatment of compounds of formula XXXIV, with compounds of formula XXXV (wherein Ri is as defined in formula I), e.g. in the presence of NaBH(OAc)s or NaBHsCN, in a suitable solvent, preferably in acetic acid at room temperature analog to W02002 / 088073, page 35. Alternatively, another reagent system for the reductive amination uses a combination of Ti(i-OiPr)s and NaBH: (see Synthesis 2003 (14), 2206). Amines of formula XXXIV can be prepared by deracemization procedure method, which involves for example, a selective acylation of one enantiomer. Such an example is described more in details in Scheme 13. Scheme 13: ‘Chemoenzymatic resolution biocatalyst e.g. lipase or protease acylating agent e.g. ethyl methoxyacetate or vinyl acetate solvent e.g. ACN or TBME T=20to 100 °C XXXIV OOIVa Xq7 = Cl, Br, |, OMs, OTs or OTT Xo7 = Cl, Br, |, OMs, OTs or OT Amines of formula XXXIV may be obtained by biocatalyzed deracemization of amines of formula XXXIVa, wherein Rs, Rss, and Rsp are as in formula 1 and Xor is a leaving group such as bromine, chlorine or iodine. This may be done for instance using a lipase, e.g. Candida Antarctica lipase B or Pseudomonas fluorescens lipase, eventually in immobilized form (e.g. Novozym® 435) in presence of an acyl donor, e.g. ethyl methoxyacetate or vinyl acetate, in a suitable solvent such as acetonitrile or methyl tert-butyl ether at temperatures between 20 °C to 100 °C. Such processes are described for instance in J. Org. Chem. 2007, 72, 6918-6923 or Adv. Synth. Catal. 2007, 349, 1481-1488. The expected stereochemical outcome of such enzymatic deracemization are known of those skilled in the art and are documented in the literature, for instance in J. Org. Chem. 1991, 56, 2656-2665 or J. Am. Chem. Soc. 2015, 137, 3996-4009. Alternatively, resolution of amines of formula XXXIVa to give amines of formula XXXIV may be achieved using a chiral auxiliary, as described in Scheme 14. Scheme 14: xed Xo peptide coupling Xoy = Cl, Br, |, OMs, OTs or OTf XT Xo7 = Cl, Br, |, OMs, OTs or OTf ~~ “CO Amines of formula XXXIV can be prepared from intermediates of formula XXXVII, wherein Rs, Rsa, and Rsp are as in compounds of the formula 1, Xor is a leaving group such as bromine, chlorine or iodine, and Xi2* is a chiral auxiliary, by treatment with acids such as HCI or bases such as NaOH. Chiral auxiliaries of formula LII are for instance mandelic acid or (1R)-menthylchloroformate. Intermediates of formula XXXVII can be formed by coupling of a chiral auxiliary of formula XXXVI, wherein Xo is a leaving group, such as chlorine, with amines of the formula XXXIVa following the conditions detailed in Scheme 1. Examples of such deracemization processes are reported in the literature, for instance in J. Org. Chem. 2007, 72, 485-493. Alternatively, amines of formula XXXIV can be formed as described in Scheme 15. Scheme 15: ‘enantioselective reduction Re” NNN Mitsunobu reaction Rs” = ON ‘deprotection ZL Xo Mitsunobu reaction NA mm Ny - J Rsb Rsa XXIa XXIVa XXla OXKTIV XXla Z, = NPhth or Boc,N Xgy =Cl, Br, |, OMs, OTs or OTF Nucleophilic ‘substitution I N N Ti azide reduction XXIIa Alternatively, amines of formula XXXIV may be obtained from intermediates of formula XXlla, wherein Rs, Rse, and Rsp are as described in formula |, Xo7 is a leaving group such as a halogen or sulfonate, for instance bromide, and Zs is NPhth or NBocz. Such intermediates can be obtained from alcohols of formula XXIa, wherein Rs, Rss, and Rsp are as described in formula | and Xo7 is a leaving group, by a Mitsunobu reaction, which involves treating alcohols of formula XXla with diisopropyl azodicarboxylate in the presence of a phosphine such as triphenylphosphine or tributylphosphine and of an amine such as phthalimide or bis(tert-butoxycarbonyl)amine. Mitsunobu reactions are known by those skilled in the art to proceed with inversion of the stereocenter, as described for instance in Chem. Rev. 20089, 109, 2551-2651. Amines of formula LIII can then be transformed into amines of formula lid by treatment with hydrazine if Za = NPhth or with TFA if Zs = NBoca. Alternatively, amines of formula XXXIV may be obtained by reduction of azides of formula XXIlla, wherein Rs, Rsa, and Rsv are as described in formula | and Xor is a leaving group such as a halogen or sulfonate, for instance bromide, by treatment with triphenylphosphine and water (Staudinger reaction) or by hydrogenation for example using a palladium catalyst in the presence of hydrogen. Azides of formula XXIlla may be obtained by treatment of alcohols of formula XXla with an azidation reagent such as diphenyl phosphoryl azide in a solvent such as toluene or THF in presence of a base such as DBU. Such processes are known by those skilled in the art to proceed with inversion of the stereocenter and are described in the literature for instance in Adv. Synth. Catal. 2018, 360, 2157— 2165. Alcohols of formula XXla may be obtained by enantioselective reduction of ketones of formula XXIVa, wherein Rs, Rss, and Reb are as described in formula | and Xor is a leaving group such as a halogen or sulfonate, for instance bromide. Such reductions can be done using catalysts, for instance a ruthenium or a rhodium catalyst with a chiral ligand such as RuCI[(R, R)-TsDPEN](mesitylene) or RuBF4[(R,R)- TsDPEN](p-cymene) in the presence of a hydrogen donor system such as for example HCOOH / EtsN or HCO2NHa. Such processes are described in the literature for instance in J. Org. Chem. 2017, 82, 5607. Compounds of formula Il "2 apa R2b AX As AS Ad, ve R2a hid wherein X1 is a leaving group, such as a halogen or sulfonate, for instance chloride, can be made, for example, as shown in Schemes 16-18. Scheme 16: NH; NH, NH, " R2b electrophilic R2b | CucN Rb 2 FN halogenation ON solvent, e.g. DMF ON Zz dE er. N&d, - Nt Rew, ~ YN halogenation YY solvent, e.g. DMF hi H,S0, Aq pe pret Aq pe ri Aq he mm R2a R2a R2a N-: XL cat. DMF NN NF Y soc, Rb I cl Ro A Aon cat. DMF I ph - Aq he R2a R2a XLII Ila Compounds of formula lla wherein R2a, R2b, A4 and A5 are as described in formula I, can be prepared according to reaction scheme 16. Compounds of formula XLII are either known, or they can be prepared by methods known to a person skilled in the art. For example, a compound of formula XL is reacted with an electrophilic iodinating reagent, such as N-iodosuccinimide, in a solvent, such as hexafluoroisopropanol, as described for example in J. Org. Chem. 2018, 83, 930, to obtain compounds of formula XLI. Cyanation of compounds of formula XLI with copper(l) cyanide in a solvent, such as DMF, at temperatures such as 100 °C, provides compounds of formula XLII (procedure analog to WO2005 / 100298, page 44). Treatment of compounds of formula XLII with formic acid and sulfuric acid at temperatures between 80 and 100 °C, provides compounds of formula XLIII (procedure analog to WO2018 / 206539, page 80). Subsequent conversion to compounds of formula lla is accomplished via according to methods known to the person skilled in the art, for example with thionyl chloride in presence of catalytic N,N-dimethylformamide at reflux, analog to WO2015 / 54572, page 263. Scheme 17: 1) SO,CINCO, solvent, e.g. DCM 2)H,0 NTR” CoH POCI, NH2 2 ra AP Ag AS - Aq AS _ Ag AS optionally in the presence of a Pig Yi base, e.g. IPrNEt Raz R2a R2a base, e.g. PrNEt R2a xn LIV mb Compounds of formula lib wherein R2a, R2b, A4 and AS5 are as described in formula I, can be prepared according to reaction scheme 17. A compound of formula XLII, prepared as in Scheme 16, is reacted with chlorosulfonyl isocyanate, then further reacted with water at reflux, as described for example in Synth. Commun. 1988, 18, 525, to provide intermediates of formula XLIV. Subsequent conversion of intermediates of formula XLIV to to compounds of formula lla is accomplished using chlorinating reagents, such as POCIs, optionally in the presence of base, such as N,N- diisopropylethylamine. These chlorinating methods are well known to the person skilled in the art. Scheme 18: NH, R2b. 1 xX Me AS R2a Ph,0 CH(OMe), JES XL YY reflux X JL phe R2a XLV XLVI CH(OMe), oO o J | MeO XLV N= NZ R2b R2b 7 OH Poly dA Cl A4 eh - gh R2a R2a XLVI IIc Compounds of formula lic wherein R2a, R2b, A4 and A5 are as described in formula |, can be prepared according to reaction scheme 18, analog to procedures found in ChemCatChem 2017, 10, 965. Meldrum’s acid is converted to compound XLV by refluxing in trimethyl orthoformate and further converted to compounds of formula XLVI in the same pot by addition of anilines of formula XL. Compounds of formula XLVI are refluxed in diphenyl ether to obtain 4-hydroxyquinolines of formula XLVII. Compounds of formula lic are then obtained via chlorination of compounds of formula XLVII using chlorinating reagents, such as POCIs, well known to the person skilled in the art. Compounds of formula Vc Ad, ee R2a Ve can be made, for example, as shown in Scheme 19. Scheme 19: XLVI A. NG Z R2b “NP AN R2b. pt - pt R2a R2a XLII Ve Compounds of formula [Vc wherein Z is H, C1-Cs alkyl, cyclopropyl, CFs, R2a, R2b, A4 and A5 are as described in formula 1, can be prepared according to reaction scheme 20. Compounds of formula XLII, prepared as in Scheme 186, are reacted in the presence of compounds of formula XLVII| at elevated temperatures, such as 180 °C, as described for example in Eur. J. Med. Chem. 2017, 141, 446, to provide amines of formula IVc. Alternatively, compounds of the formula lab can be made, for example, as shown in Scheme 20. Scheme 20: m OMe Sone NHz rao on AN nv 7 R2b. CN . lh R3 R26 pp od A4 AS Ri ey AS A4 tps solvent. e.g. acetic acld My AS R2a R2a R2a Xoo XLVIID Ie Compounds of formula lab, wherein R1, R2a, R2b, R3, A4, A5, Q are as described in formula |, can be prepared according to scheme 21, analog to the procedures in WO2010 / 093419, page 225. Compounds of formula XLII, prepared as in Scheme 16, are treated with N,N-dimethylformamide dimethyl acetal at elevated temperature, preferably 90 °C, to provide formamidine products of formula XLVIII. Reaction with amines of formula II] at elevated temperature, preferably 120 °C, in a suitable solvent, preferably acetic acid, provides compounds of formula lab. Compounds of the formula If OMe OMe YE R2b. SA Aq AS R1 Mere R2a If can be made, for example, as shown in Scheme 21. Scheme 21: base, e.g. NaH, K,CO; I, + x x I 1 NEN NEN Re HOON RS meyisngagent NN Re ] uw [LL wnsn mesa ] J ] . 5 metry sutate me A a LN ro A ra ro A ra a he ds ok ae as hq beseeg NaHCO, J LL A w OL kw BAS ALAS RT AL As RY TTRERTIRIETR a4 AS T T T T Ria A J. on Compounds of formula If, wherein R1, R2a, R2b, R3, A4, A5, Q are as described in formula I, can be prepared according to Scheme 21. Reaction of compounds of formula lib, prepared as in Scheme 17, with amines of formula Ill, using procedures presented in Scheme 1, provides compounds of formula le. Treatment of compounds of formula le under acidic conditions, preferably with acetic acid, at elevated temperatures, preferably between 70 and 80 °C, as described in Heterocycles 1996, 43, 2607, provides intermediates of formula LI. Methylation of compounds of formula LI to obtain compounds of formula If can be achieved using an electrophilic methyl sources, such as dimethyl sulfate or methyl iodide, in the presence of a base, such potassium carbonate or sodium hydride, as well known to the person skilled in the art. Compounds of the formula Ig “7 R2b. SN Aq AS R1 Mate R2a If can be made, for example, as shown in Scheme 22. Scheme 22: camynittte R2b, CN DBALH R2b CHO Trimethyisiiyiacetylene CHaly Ry solvent, e.g. toluene gl ‘Sonogashira NH R2b. CN Isoamyhnitrte R2b, CN A ini A R2b. CHO Ad _AS T+ Ad AST Ad _ AS T T T R2a R2a R2a XLO 1X x1 ‘oxidant ZN R2b. J x iMes R24 CHO NH, inMeOH My AS My AS Roa Roa > OR a Ri Nm AN m R2b A a Apts activating agent, e.g. PyBroP® Agihe R1 R2a R2a 2 - HNNQ oxidant eC 7 sohert | 6.9, dichloromethane R20. A m - i — rhe sclhating agent, e.g. Roa LXI Xm LXIV Ig Compounds of formula Ig, wherein R1, R2a, R2b, R3, A4, A5, Q are as described in formula |, can be prepared according to Scheme 22. A compound of formula XLII, as prepared in Scheme 18, is treated with a diazotizing reagent, preferably isoamylnitrite, in diiodomethane solvent, at elevated temperature, preferably 80 °C, as described in J. Org. Chem. 1990, 55, 2543, to provide intermediates of formula LX. Reduction of compounds of formula LX is achieved in the presence of a selective reductant, such as diisobutylaluminum hydride (DIBALH), in a solvent, such as toluene, at low temperatures, preferably -78 °C, and gives a compound of formula LXI. Subsequent Sonogashira coupling in the presence of suitable palladium and copper catalysts, preferably bis(triphenylphosphine)palladium chloride and copper(I) iodide, with trimethylsilylacetylene, in a solvent, such as triethylamine, gives compounds of formula LXII. Cyclization with ammonia in methanol gives compounds of formula LXIII. Procedures are analog to those described for example in Eur. J. Med. Chem. 2016, 118, 170. Treatment of compounds of formula LXIII with an oxidant, such as 3-chloro-benzenecarboperoxoic acid or hydrogen peroxide, in a solvent, preferably dichloromethane, gives N-oxides of formula LXIV. Such oxidations are well known to the person skilled in the art. Coupling of compounds of formula LXIV with amines of formula Ill in the presence of a suitable activator, such as bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP®), potentially in the presence of base, such as N,N-diisopropylethylamine, analog to procedure described in WO2016 / 123627, page 87, gives compounds of formula Ig. Compounds of formula lid NN | R2b | NY A4 Na R2a od wherein X1 is a leaving group, such as a halogen or sulfonate, for instance chloride, can be made, for example, as shown in Scheme 23. Scheme 23: Tributyl(1-ethoxyvinytin Nez NH2 O NY NY 1) Pa(ePhg, catalyst Rb AA A re A Acs, [RL AN SoH Pocl, R2b Aa Ad AST oa A4___AS TT AMA p oe! A4___AS 2HCI = = optional inthe presence ofa 4. IT hl hl Sas. e.g. FENEL IT R2a R2a R2a R2a nd Compounds of formula Id, wherein R2a, R2b, A4, AS are as described in formula |, can be prepared according to Scheme 23. A compound of formula XLI, as prepared in Scheme 16, is treated with a palladium catalyst, preferably Pd(PPha)s, along with tributyl(1-ethoxyvinyltin, at elevated temperature, preferably 105 °C, as described in EP1782811, page 57, to provide intermediates of formula LXV. Treatment of compounds of formula LXV with aqueous sodium nitrite in the presence of acids, such as hydrochloric acid or a sulfuric acid / acetic acid mixture at low temperatures, preferably between 0 and 5 °C, analog to Bioorg. Med. Chem. Lett., 25, 918, gives compounds of formula LXVI. Compounds of formula lid are then obtained via chlorination of compounds of formula LXV! using chlorinating reagents, such as POCIs, optionally in the presence of an amine base, such as N,N- diisopropylethylamine, well known to the person skilled in the art. Compounds of formula lle N = NNT R2b | NX AAS Ag R2a nd wherein X1 is a leaving group, such as a halogen or sulfonate, for instance chloride, can be made, for example, as shown in Scheme 24. Scheme 24: NH R25 Na [ 0 H w oN N Z Ny NY RN oH soc ove FPN ALAS AQ AS NT LLY . — p eating / solvent oe oe R2a T yp R2a R2a Te Compounds of formula lle, wherein R2a, R2b, A4, AS are as described in formula |, can be prepared according to Scheme 24. A compound of formula XL is heated with ethyl 2-cyano-3-ethoxyacrylate at elevated temperature, preferably 140 °C, as described in Tetrahedron Letters, 2015, 56, 5112, to provide intermediates of formula LXVII. Heating of compounds of formula LXVII at elevated temperatures, preferably between at 260 °C, in a solvent, preferably diphenyl ether or diphenyl ether- biphenyl eutectic mixture (Dowtherm A®), gives compounds of formula LXVIII. Subsequent conversion to compounds of formula Ile is accomplished via according to methods known to the person skilled in the art, for example with thionyl chloride in presence of catalytic N,N-dimethylformamide at reflux, analog to US2003 / 212276, page 15. Compounds of the formula Ih N. aE: R2b. A Ad A5 R1 Mp he R2a Th can be made, for example, as shown in Scheme 25. Scheme 25: ur NHz NH rh R2b, oN R2b R2b PN H,0,, base SY ONHz NaNO, acid Ao a oN NHz Ny § S N? WN Tr R2b. R2b. R2b. H,0; base NY NH: NaNO, acd Ro PyBOP® SS Q = Ad AS = A4__AS = A4__AS RI i - pte - Ape - photo R2 R2 R2 R22 XL IXX >xXx1 Th Compounds of formula Ih, wherein R1, R2a, R2b, R3, A4, A5, Q are as described in formula |, can be prepared according to Scheme 25. A compound of formula XLII, as prepared in Scheme 16, is treated with hydrogen peroxide, either as an aqueous solution or as an urea adduct, in methanol-water solvent, in the presence of base, preferably potassium carbonate, analog to WO2011 / 4276, page 132, to provide intermediates of formula LXX. Treatment of compounds of formula LXX with aqueous sodium nitrite in the presence of acids, such as hydrochloric acid or a sulfuric acid / acetic acid mixture at low temperatures, preferably between 0 and 5 °C, analog to US2014 / 0275072, paragraph 133, gives compounds of formula LXXI. Coupling of compounds of formula LXXI with amines of formula [lI in the presence of a suitable activator, such as (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBoP®), in the presence of base, such as N,N-diisopropylethylamine, analog to procedure described in WO2014 / 085528, page 55, gives compounds of formula Ih. Compounds of the formula li F rR Rb A a Ad _A5 R11 Me AS R2a Th can be made, for example, as shown in Scheme 26. Scheme 26: Selectfluor NZ ] . R3 R2b A PS Ad _ AS 1 NZ R3 R2b A J " Ae I A4 AS #1 A4 _A5 R1 - A4 AS T T R2a R2a laa Ii Compounds of formula li, wherein R1, R2a, R2b, R3, A4, A5, Q are as described in formula |, can be prepared according to Scheme 26. A compound of formula laa, as prepared in Scheme 1, 5 or 6, is treated with a fluorinating reagent, preferably 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor), in a solvent, preferably acetonitrile, analog to WO2018 / 34917, page 91, to provide compounds of formula Ii. Compounds of the formula Ij Cl TR EN va Ad _A5 R1 rhe R2a 5 can be made, for example, as shown in Scheme 27. Scheme 27: N-Chlorosuccinimide Cl NZ ] R3 R2b A y Ae Ad AS 1 NZ ] R3 R2b, NS re Ad __A5 R1 cat. DMSO A4 AS R1 ” A4 AS hp cat. DMSO Y R2a R2a laa Ij Compounds of formula Ij, wherein R1, R2a, R2b, R3, A4, A5, Q are as described in formula |, can be prepared according to Scheme 27. A compound of formula laa, as prepared in Scheme 1, 5 or 6, is treated with a chlorinating reagent, preferably N-chlorosuccinimide, in the presence of catalytic dimethyl sulfoxide (DMSO), in a solvent, preferably dichloromethane, analog to Nature Catalysis, 2020, 3, 107, to provide compounds of formula lj. Compounds of the formula Im Sy Hz R3 A2 AY ne R3 Y R2b NS . | H IN H UI NA oll R2a Im can be made, for example, as shown in Scheme 28. Scheme 28: SN Hy R3 NN _N A1° A3 R3 optionally with base =) r—\ A2 I A2 AT” TAZ Re 2 AT” TA3 Rs § | | | ammonium sulfide Ra AANA - Hgts R1 NA pyridine he R1 NA optionally with base R2a ; R2a i. ek eS Im Compounds of formula Im, wherein R1, R2a, R2b, R3, A1, A2, A3, A4, AS are as described in formula 1, can be prepared according to Scheme 28. A compound of formula Ik, as prepared in Scheme 1, 3, 5, 6, 20, 21, 22, 25, 26, or 27, is treated with ammonium sulfide, in a solvent, preferably pyridine, optionally in the presence of a base, preferably triethylamine, analog to WO2017 / 192385 page 60, to provide compounds of formula Im. Compounds of the formula In Li ~% S. Nn s WN H N > aps R3 N= ro AN ANN Re N L H | / Ad AS Nn Me AS R2a In can be made, for example, as shown in Scheme 29. Scheme 29: Br— F o °F trifluoroacetic anhydride triethylamine AAS I hoa SNH; > Br— A2 i aur NA JI < rn A Ap roto kind fem Compounds of formula In, wherein R1, R2a, R2b, R3, A1, A2, A3, A4, AS are as described in formula 1, can be prepared according to Scheme 29. A compound of formula Im, as prepared in Scheme 28, is reacted with 3-bromo-1,1,1-trifluoroacetone, in a solvent, preferably N,N-dimethyiformamide or acetonitrile, analog to W0O2010 / 136817, page 110, to provide compounds of formula LXXII. Treatment of compounds of formula LXXII with trifluoroacetic anhydride, in the presence of base, preferably triethylamine, in a solvent, preferably tetrahydrofuran or acetonitrile, analog to J. Med. Chem., 2013, 56, 8712, gives compounds of formula In. Depending on the procedure or the reaction conditions, the reactants can be reacted in the presence of a base. Examples of suitable bases are alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamines, alkylenediamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N- dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N- methylmorpholine, benzyltrimethylammonium hydroxide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The reactants can be reacted with each other as such, i.e. without adding a solvent or diluent. In most cases, however, it is advantageous to add an inert solvent or diluent or a mixture of these. If the reaction is carried out in the presence of a base, bases which are employed in excess, such as triethylamine, pyridine, N-methylmorpholine or N,N-diethylaniline, may also act as solvents or diluents. The reactions are advantageously carried out in a temperature range from approximately -80°C to approximately +140°C, preferably from approximately -30°C to approximately +100°C, in many cases in the range between ambient temperature and approximately +80°C. Depending on the choice of the reaction conditions and starting materials which are suitable in each case, it is possible, for example, in one reaction step only to replace one substituent by another substituent according to the invention, or a plurality of substituents can be replaced by other substituents according to the invention in the same reaction step. Salts of compounds of formula | can be prepared in a manner known per se. Thus, for example, acid addition salts of compounds of formula | are obtained by treatment with a suitable acid or a suitable ion exchanger reagent and salts with bases are obtained by treatment with a suitable base or with a suitable ion exchanger reagent. Salts of compounds of formula | can be converted in the customary manner into the free compounds I, acid addition salts, for example, by treatment with a suitable basic compound or with a suitable ion exchanger reagent and salts with bases, for example, by treatment with a suitable acid or with a suitable ion exchanger reagent. Salts of compounds of formula | can be converted in a manner known per se into other salts of compounds of formula |, acid addition salts, for example, into other acid addition salts, for example by treatment of a salt of inorganic acid such as hydrochloride with a suitable metal salt such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in a suitable solvent in which an inorganic salt which forms, for example silver chloride, is insoluble and thus precipitates from the reaction mixture. Depending on the procedure or the reaction conditions, the compounds of formula I, which have salt- forming properties can be obtained in free form or in the form of salts. The compounds of formula | and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can be present in the form of one of the isomers which are possible or as a mixture of these, for example in the form of pure isomers, such as antipodes and / or diastereomers, or as isomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and / or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure isomers and also to all isomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case. Diastereomer mixtures or racemate mixtures of compounds of formula |, in free form or in salt form, which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diasteromers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and / or chromatography. Enantiomer mixtures, such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high-performance liquid chromatography (HPLC) on acetyl celulose, with the aid of suitable microorganisms, by cleavage with specific, immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is complexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities, to give the diastereomers, from which the desired enantiomer can be set free by the action of suitable agents, for example basic agents. Pure diastereomers or enantiomers can be obtained according to the invention not only by separating suitable isomer mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials of a suitable stereochemistry. N-oxides can be prepared by reacting a compound of the formula | with a suitable oxidizing agent, for example the H202 / urea adduct in the presence of an acid anhydride, e.g. trifluoroacetic anhydride. Such oxidations are known from the literature, for example from J. Med. Chem., 32 (12), 2561-73, 41989 or WO 2000 / 15615. It is advantageous to isolate or synthesize in each case the biologically more effective isomer, for example enantiomer or diastereomer, or isomer mixture, for example enantiomer mixture or diastereomer mixture, if the individual components have a different biological activity. The compounds of formula | and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can, if appropriate, also be obtained in the form of hydrates and / or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form. The compounds of formula | according to the following Tables D-1 to D-66 can be prepared according to the methods described above. The examples which follow are intended to illustrate the invention and show preferred compounds of formula |, in the form of a compound of formula I-D. f formula 1, in the form of a compo Ap AZ k Rob, 2 SN A R, | Fm | Ra CN Ci NF —N cl XN N Cl cl Table D-2 provides 12 compounds D-2.001 to D-2.012 of formula |-D wherein A1 is N, Azis CH, Asis CH, Asis CH, Asis CH, R1is CHa, Raa is Cl, Rav is Cl, and Q is as defined in table Z. Table D-3 provides 12 compounds D-3.001 to D-3.012 of formula |-D wherein A1 is N, Azis CH, Aa is CH, Asis CH, Asis CH, Ry is CHz-cyclopropyl, Rza is Cl, Ran is Cl, and Q is as defined in table Z. Table D-4 provides 12 compounds D-4.001 to D-4.012 of formula I-D wherein A1 is N, Azis CH, Asis N, Asis CH, Asis CH, Ry is H, Rza is Cl, Rzp is Cl, and Q is as defined in table Z. Table D-5 provides 12 compounds D-5.001 to D-5.012 of formula I-D wherein Ais N, Azis CH, Asis N, A4is CH, Asis CH, R;is CHa, Rza is Cl, Rav is Cl, and Q is as defined in table Z. Table D-6 provides 12 compounds D-6.001 to D-6.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, As is CH, Ri is CHz-cyclopropyl, Rza is Cl, Rab is Cl, and Q is as defined in table Z. Table D-7 provides 12 compounds D-7.001 to D-7.012 of formula |-D wherein A1 is N, Azis CH, As is CH, A4is CH, Asis CH, R1 is H, Rza is CF3, Ran is CFs, and Q is as defined in table Z. Table D-8 provides 12 compounds D-8.001 to D-8.012 of formula |-D wherein A1 is N, Azis CH, As is CH, Asis CH, Asis CH, Riis CHa, Raa is CFs, Rav is CFs, and Q is as defined in table Z. Table D-9 provides 12 compounds D-9.001 to D-9.012 of formula I-D wherein A1 is N, Azis CH, Asis CH, Asis CH, Asis CH, Ry is CHz-cyclopropyl, Rza is CFs, Rap is CF3, and Q is as defined in table Z. Table D-10 provides 12 compounds D-10.001 to D-10.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, Asis CH, R1 is H, Rza is CF3, Rap is CF3, and Q is as defined in table Z. Table D-11 provides 12 compounds D-11.001 to D-11.012 of formula I-D wherein Asis N, Azis CH, As is N, Asis CH, Asis CH, Rp is CHa, Raza is CF3, Rap is CFa, and Q is as defined in table Z. Table D-12 provides 12 compounds D-12.001 to D-12.012 of formula I-D wherein Asis N, Azis CH, As is N, Asis CH, As is CH, Ry is CHz-cyclopropyl, Rza is CF3, Rap is CF3, and Q is as defined in table Z. Table D-13 provides 12 compounds D-13.001 to D-13.012 of formula I-D wherein Asis N, Azis CH, As is CH, Asis CH, Asis CH, R1 is H, Rza is CF3, R2p is Cl, and Q is as defined in table Z. Table D-14 provides 12 compounds D-14.001 to D-14.012 of formula |-D wherein A1 is N, Azis CH, As is CH, Asis CH, Asis CH, R; is CHa, Rz2a is CFa, Rap is Cl, and Q is as defined in table Z. Table D-15 provides 12 compounds D-15.001 to D-15.012 of formula |-D wherein A1 is N, Azis CH, As is CH, Asis CH, As is CH, Ry is CH2-cyclopropyl, Rza is CF3, Rap is Cl, and Q is as defined in table Z. Table D-16 provides 12 compounds D-16.001 to D-16.012 of formula |-D wherein A1 is N, Azis CH, Aa is N, Asis CH, As is CH, Ry is H, Raza is CF3, Rav is Cl, and Q is as defined in table Z. Table D-17 provides 12 compounds D-17.001 to D-17.012 of formula |-D wherein Aq is N, Azis CH, As is N, Asis CH, Asis CH, Riis CHs, Rza is CFs, Rap is Cl, and Q is as defined in table Z. Table D-18 provides 12 compounds D-18.001 to D-18.012 of formula I-D wherein Asis N, Azis CH, As is N, Asis CH, As is CH, Ry is CHz-cyclopropyl, Rza is CFs, Rzp is Cl, and Q is as defined in table Z. Table D-19 provides 12 compounds D-19.001 to D-19.012 of formula I-D wherein Aris N, Azis CH, As is CH, Asis CH, Asis CH, R1 is H, Rza is Cl, Rzn is CF3, and Q is as defined in table Z. Table D-20 provides 12 compounds D-20.001 to D-20.012 of formula |-D wherein A1 is N, Azis CH, Aa is CH, Asis CH, Asis CH, R:is CHa, Rza is Cl, Rav is CF3, and Q is as defined in table Z. Table D-21 provides 12 compounds D-21.001 to D-21.012 of formula |-D wherein A1 is N, Azis CH, Aa is CH, Asis CH, As is CH, Ri is CHz-cyclopropyl, Raza is Cl, Ras is CF3, and Q is as defined in table Z. Table D-22 provides 12 compounds D-22.001 to D-22.012 of formula I-D wherein Asis N, Azis CH, As is N, Asis CH, Asis CH, Rs is H, Rza is Cl, Rap is CF3, and Q is as defined in table Z. Table D-23 provides 12 compounds D-23.001 to D-23.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, Asis CH, Riis CHs, Raza is Cl, Rzp is CFs, and Q is as defined in table Z. Table D-24 provides 12 compounds D-24.001 to D-24.012 of formula |-D wherein Aq is N, Azis CH, As is N, As is CH, As is CH, R; is CHz-cyclopropyl, Rza is Cl, Rzp is CF3, and Q is as defined in table Z. Table D-25 provides 12 compounds D-25.001 to D-25.012 of formula I-D wherein Asis N, Azis CH, As is CH, Asis CH, Asis CH, R1 is H, Rza is Cl, Rzp is Br, and Q is as defined in table Z. Table D-26 provides 12 compounds D-26.001 to D-26.012 of formula I-D wherein Asis N, Azis CH, As is CH, Asis CH, Asis CH, R;is CHs, Rza is Cl, Rzp is Br, and Q is as defined in table Z. Table D-27 provides 12 compounds D-27.001 to D-27.012 of formula |-D wherein A1 is N, Azis CH, As is CH, Asis CH, As is CH, Ry is CH2-cyclopropyl, Raza is Cl, Ras is Br, and Q is as defined in table Z. Table D-28 provides 12 compounds D-28.001 to D-28.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, As is CH, Rs is H, Rz2a is Cl, Ray is Br, and Q is as defined in table Z. Table D-29 provides 12 compounds D-29.001 to D-29.012 of formula |-D wherein A1 is N, Azis CH, Aa is N, Asis CH, As is CH, Riis CHa, Raza is Cl, Rap is Br, and Q is as defined in table Z. Table D-30 provides 12 compounds D-30.001 to D-30.012 of formula |-D wherein Aq is N, Azis CH, As is N, Asis CH, As is CH, Ry is CHz-cyclopropyl, Rza is Cl, Raz is Br, and Q is as defined in table Z. Table D-31 provides 12 compounds D-31.001 to D-31.012 of formula I-D wherein Aris N, Azis CH, As is CH, Asis CH, Asis CH, R1 is H, Rza is Br, Ran is Cl, and Q is as defined in table Z. Table D-32 provides 12 compounds D-32.001 to D-32.012 of formula |-D wherein Aq is N, Azis CH, As is CH, Asis CH, Asis CH, R;is CHs, Rzq is Br, Rap is Cl, and Q is as defined in table Z. Table D-33 provides 12 compounds D-33.001 to D-33.012 of formula |-D wherein A1 is N, Azis CH, Aa is CH, Asis CH, As is CH, Ri is CH2-cyclopropyl, Raza is Br, Rap is Cl, and Q is as defined in table Z. Table D-34 provides 12 compounds D-34.001 to D-34.012 of formula |-D wherein A1 is N, Azis CH, Aa is N, Asis CH, Asis CH, R1 is H, Raza is Br, Rav is Cl, and Q is as defined in table Z. Table D-35 provides 12 compounds D-35.001 to D-35.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, Asis CH, Riis CHs, Raza is Br, Rap is Cl, and Q is as defined in table Z. Table D-36 provides 12 compounds D-36.001 to D-36.012 of formula I-D wherein As is N, Azis CH, As is N, Asis CH, As is CH, Ry is CHz-cyclopropyl, Rza is Br, Rzp is Cl, and Q is as defined in table Z. Table D-37 provides 12 compounds D-37.001 to D-37.012 of formula |-D wherein A1 is N, Azis CH, As is CH, Asis CH, Asis CH, R1 is H, Rza is CF3, Rzp is Br, and Q is as defined in table Z. Table D-38 provides 12 compounds D-38.001 to D-38.012 of formula I-D wherein Asis N, Azis CH, As is CH, Asis CH, Asis CH, R;is CHa, Rza is CFs, Rap is Br, and Q is as defined in table Z. Table D-39 provides 12 compounds D-39.001 to D-39.012 of formula I-D wherein Asis N, Azis CH, As is CH, Asis CH, As is CH, R1 is CHz-cyclopropyl, Rza is CFs, Raz is Br, and Q is as defined in table Z. Table D-40 provides 12 compounds D-40.001 to D-40.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, As is CH, Ry is H, Raza is CF3, Rap is Br, and Q is as defined in table Z. Table D-41 provides 12 compounds D-41.001 to D-41.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, As is CH, Riis CHa, Raza is CF3, Rap is Br, and Q is as defined in table Z. Table D-42 provides 12 compounds D-42.001 to D-42.012 of formula |-D wherein A1 is N, Azis CH, Aa is N, Asis CH, As is CH, Ry is CHz-cyclopropyl, Rza is CFa, Rab is Br, and Q is as defined in table Z. Table D-43 provides 12 compounds D-43.001 to D-43.012 of formula I-D wherein Aris N, Azis CH, As is CH, Asis CH, Asis CH, R1 is H, Rz2a is Br, Rap is CF3, and Q is as defined in table Z. Table D-44 provides 12 compounds D-44.001 to D-44.012 of formula |-D wherein Aq is N, Azis CH, As is CH, Asis CH, Asis CH, R;is CHs, Rza is Br, Rap is CFs, and Q is as defined in table Z. Table D-45 provides 12 compounds D-45.001 to D-45.012 of formula I-D wherein Asis N, Azis CH, As is CH, Asis CH, As is CH, Ry is CHz-cyclopropyl, Rza is Br, Rzp is CF3, and Q is as defined in table Z. Table D-46 provides 12 compounds D-46.001 to D-46.012 of formula |-D wherein A1 is N, Azis CH, Aa is N, Asis CH, As is CH, R; is H, Raza is Br, Rav is CF3, and Q is as defined in table Z. Table D-47 provides 12 compounds D-47.001 to D-47.012 of formula |-D wherein A1 is N, Azis CH, Aa is N, Asis CH, Asis CH, R1is CHa, Raza is Br, Rav is CFa, and Q is as defined in table Z. Table D-48 provides 12 compounds D-48.001 to D-48.012 of formula I-D wherein Asis N, Azis CH, As is N, Asis CH, As is CH, Ry is CHz-cyclopropyl, Rza is Br, Rzp is CFs, and Q is as defined in table Z. Table D-49 provides 12 compounds D-49.001 to D-49.012 of formula I-D wherein Aris N, Azis CH, As is CH, Asis CH, Asis CH, R1 is H, Rza is Br, Rap is Br, and Q is as defined in table Z. Table D-50 provides 12 compounds D-50.001 to D-50.012 of formula |-D wherein Aq is N, Azis CH, As is CH, Asis CH, Asis CH, Rj is CHa, Rzais Br, Rav is Br, and Q is as defined in table Z. Table D-51 provides 12 compounds D-51.001 to D-51.012 of formula I-D wherein Asis N, Azis CH, As is CH, Asis CH, As is CH, Ry is CHz-cyclopropyl, Raza is Br, Rzp is Br, and Q is as defined in table Z. Table D-52 provides 12 compounds D-52.001 to D-52.012 of formula I-D wherein Asis N, Azis CH, As is N, Asis CH, Asis CH, Ry is H, Ra is Br, Rzp is Br, and Q is as defined in table Z. Table D-53 provides 12 compounds D-53.001 to D-53.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, As is CH, Rj is CHa, Raza is Br, Rzp is Br, and Q is as defined in table Z. Table D-54 provides 12 compounds D-54.001 to D-54.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, As is CH, Ry is CHz-cyclopropyl, Rza is Br, Rzp is Br, and Q is as defined in table Z. Table D-55 provides 12 compounds D-55.001 to D-55.012 of formula |-D wherein A1 is N, Azis CH, As is CH, Asis CH, Asis CH, R1 is H, Rza is CF3, Rap is |, and Q is as defined in table Z. Table D-56 provides 12 compounds D-56.001 to D-56.012 of formula |-D wherein Aq is N, Azis CH, As is CH, Asis CH, Asis CH, R;is CHa, Rza is CF3, Rap is |, and Q is as defined in table Z. Table D-57 provides 12 compounds D-57.001 to D-57.012 of formula |-D wherein Aq is N, Azis CH, As is CH, Asis CH, As is CH, Ry is CHz-cyclopropyl, Rza is CFs, Rap is |, and Q is as defined in table Z. Table D-58 provides 12 compounds D-58.001 to D-58.012 of formula |-D wherein Aq is N, Azis CH, As is N, Asis CH, Asis CH, Ry is H, Rza is CF3, Rap is |, and Q is as defined in table Z. Table D-59 provides 12 compounds D-59.001 to D-59.012 of formula |-D wherein A1 is N, Azis CH, Aa is N, Asis CH, Asis CH, Riis CHa, Rz2s is CF3, Rais |, and Q is as defined in table Z. Table D-60 provides 12 compounds D-80.001 to D-60.012 of formula |-D wherein A1 is N, Azis CH, Aa is N, Asis CH, As is CH, Ri is CHz-cyclopropyl, Rza is CFa, Rap is |, and Q is as defined in table Z. Table D-61 provides 12 compounds D-61.001 to D-61.012 of formula I-D wherein Aris N, Azis CH, As is CH, Asis CH, Asis CH, Riis H, R2a is |, Rav is CF3, and Q is as defined in table Z. Table D-62 provides 12 compounds D-62.001 to D-62.012 of formula |-D wherein A1 is N, Azis CH, As is CH, Asis CH, Asis CH, Riis CHa, Raa is |, Rap is CFs, and Q is as defined in table Z. Table D-63 provides 12 compounds D-63.001 to D-63.012 of formula |-D wherein Aq is N, Azis CH, As is CH, Asis CH, As is CH, Ry is CHz-cyclopropyl, Rza is |, Ra» is CF3, and Q is as defined in table Z. Table D-64 provides 12 compounds D-64.001 to D-64.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, Asis CH, Riis H, Rza is |, Rab is CF3, and Q is as defined in table Z. Table D-65 provides 12 compounds D-65.001 to D-65.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, Asis CH, R1is CHa, Raa is |, Rp is CF3, and Q is as defined in table Z. Table D-66 provides 12 compounds D-66.001 to D-66.012 of formula |-D wherein A1 is N, Azis CH, As is N, Asis CH, As is CH, Ri is CHz-cyclopropyl, Rza is |, Rab is CF3, and Q is as defined in table Z. Table Z: Substituent definitions of Q: Index Q Index Q my N\=N N I Sp I N= N NS Ar Nt 2 CN 8 cN 7 Il I! N= N NA fr 3 Br 9 Br Br J | / N= N NT ay Index Q Index Q ' 4 Br 10 EF I I N= N NU 5 BE 1 F mn F 1 Ne oN, I NA N Nd AN NW fa PR TY Co : NZ EN NN NX " N NU ’ for iN N Ny Br Also made available are certain intermediate compounds of formulae 11(j), 11), IV(), V(), VII), XI), and XIV(i), some of which are novel. For example, A compound of formula I1(i), wherein (i) X1 is Cl and As, Az, As, As, As, R2s and Rap are as defined in any one Tables D-1 to D-66; (ii) wherein (i) X1 is Br and Ai, Az, As, A4, As, R2a and Razp are as defined in any one Tables D-1 to D-66. A2 NY R2b | Nx Ad _AS A4___AS YY R2a 130) A compound of formula I1i(i), wherein (i) R1 is Hand Q is as defined in table Z; (ii) wherein (i) R1 is CHs and Q is as defined in table Z; and (iii) wherein (i) R1 is CHz-cyclopropyl and Q is as defined in table Z. HN 1 R1 1G) A compound of formula IV()), wherein A1, Az, As, As, As, Rza and Ras are as defined in any one Tables D-1 to D-66. A2 AAs R2b NY ONH, A4 __AS ~F R2a IV) A compound of formula V(i), wherein (i) X2 is Cland Q is as defined in table Z; (ii) wherein (i) X2 is Brand Q is as defined in table Z; and (iii) wherein (i) X2 is | and Q is as defined in table Z. x2 ~a V(i) A compound of formula VII(i), wherein Q is as defined in table Z. oa VII) A compound of formula XI(i), wherein A1, Az, As, A4, As, R1, R2a and Rav are as defined in any one Tables D-1 to D-66. A: AT “4 o REA } : I | _As Ry N Mr 5 1 S Roa NC XI) A compound of formula XIV(i), wherein Ax, Az, As, A4, As, R1, Raa and Rzb are as defined in any one Tables D-1 to D-66. A AF Zag ¢l Rob NIWA 4! _ 1 R LA 1 Aa he 1 NA Roa XIV(3) In further aspect, the present invention accordingly makes available compounds of formulae II), 111i), VG), VG), VIG), XI), and XIV(i), wherein in each case, as applicable, Ar, Az, As, As, As, R1, Rzs and Ras and Q are as defined for formula | in the first aspect; and in respect of formula I1(i), X1 is a halogen, preferably chloro or bromo. Furthermore, the corresponding embodiments illustrated for formula | also apply to the compounds of formulae 11(i), 111i), IV(D), V(i), VII), XI), and XIV(), The compounds of formula | according to the invention are preventively and / or curatively valuable ac- tive ingredients in the field of pest control, even at low rates of application, which have a very favorable biocidal spectrum and are well tolerated by warm-blooded species, fish and plants. The active ingredients according to the invention act against all or individual developmental stages of normally sensitive, but also resistant, animal pests, such as insects or representatives of the order Acarina. The insecticidal or acaricidal activity of the active ingredients according to the invention can manifest itself directly, i. e. in destruction of the pests, which takes place either immediately or only after some time has elapsed, for example during ecdysis, or indirectly, for example in a reduced oviposition and / or hatching rate. Examples of the above mentioned animal pests are: from the order Acarina, for example, Acalitus spp, Aculus spp, Acaricalus spp, Aceria spp, Acarus siro, Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia spp, Calipitrimerus spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides spp, Eotetranychus spp, Eriophyes spp., Hemitarsonemus spp, Hyalomma spp., Ixodes spp., Olygonychus spp, Ornithodoros spp., Polyphagotarsone latus, Panonychus spp., Phyllocoptruta oleivora, Phytonemus spp, Polyphagotarsonemus spp, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Steneotarsonemus spp, Tarsonemus spp. and Tetranychus spp.; from the order Anoplura, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.; from the order Coleoptera, for example, Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus spp., Aphodius spp, Astylus atromaculatus, Ataenius spp, Atomaria linearis, Chaetocnema tibialis, Cerotoma spp, Conoderus spp, Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephala spp, Dermestes spp., Diabrotica spp., Diloboderus abderus, Epilachna spp., Eremnus spp., Heteronychus arator, Hypothenemus hampei, Lagria vilosa, Leptinotarsa decemlineata, Lissorhoptrus spp., Liogenys spp, Maecolaspis spp, Maladera castanea, Megascelis spp, Melighetes aeneus, Melolontha spp., Myochrous armatus, Orycaephilus spp., Otiorhynchus spp., Phyllophaga spp, Phlyctinus spp., Popillia spp., Psylliodes spp., Rhyssomatus aubtilis, Rhizopertha spp., Scarabeidae, Sitophilus spp., Sitotroga spp., Somaticus spp, Sphenophorus spp, Sterechus subsignatus, Tenebrio spp., Tribolium spp. and Trogoderma spp.; from the order Diptera, for example, Aedes spp., Anopheles spp, Antherigona soccata,Bactrocea oleae, Bibio hortulanus, Bradysia spp, Calliphora erythrocephala, Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Delia spp, Drosophila melanogaster, Fannia spp., Gastrophilus spp., Geomyza tripunctata, Glossina spp., Hypoderma spp., Hyppobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp., Musca spp., Oestrus spp., Orseolia spp., Oscinella frit, Pegomyia hyoscyami, Phorbia spp., Rhagoletis spp, Rivelia quadrifasciata, Scatella spp, Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp. and Tipula spp.; from the order Hemiptera, for example, Acanthocoris scabrator, Acrostemum spp, Adelphocoris lineolatus, Aleurodes spp., Amblypelta nitida, Bathycoelia thalassina, Blissus spp, Cimex spp., Clavigralla tomentosicollis, Creontiades spp, Distantiella theobroma, Dichelops furcatus, Dysdercus spp., Edessa spp, Euchistus spp., Eurydema pulchrum, Eurygaster spp., Halyomorpha halys, Horcias nobilellus, Leptocorisa spp., Lygus spp, Margarodes spp, Murgantia histrionic, Neomegalotomus spp, Nesidiocoris tenuis, Nezara spp., Nysius simulans, Oebalus insularis, Piesma spp., Piezodorus spp, Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophara spp. , Thyanta spp , Triatoma spp., Vatiga illudens; Acyrthosium pisum, Adalges spp, Agalliana ensigera, Agonoscena targionii, Aleurodicus spp, Aleurocanthus spp, Aleurolobus barodensis, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca biguttula, Amritodus atkinsoni, Aonidiella spp., Aphididae, Aphis spp., Aspidiotus spp., Aulacorthum solani, Bactericera cockerelli, Bemisia spp, Brachycaudus spp, Brevicoryne brassicae, Cacopsylla spp, Cavariella aegopodii Scop., Ceroplaster spp., Chrysomphalus aonidium, Chrysomphalus dictyospermi, Cicadella spp, Cofana spectra, Cryptomyzus spp, Cicadulina spp, Coccus hesperidum, Dalbulus maidis, Dialeurodes spp, Diaphorina citri, Diuraphis noxia, Dysaphis spp, Empoasca spp., Eriosoma larigerum, Erythroneura spp., Gascardia spp., Glycaspis brimblecombei, Hyadaphis pseudobrassicae, Hyalopterus spp, Hyperomyzus pallidus, Idioscopus clypealis, Jacobiasca lybica, Laodelphax spp., Lecanium corni, Lepidosaphes spp., Lopaphis erysimi, Lyogenys maids, Macrosiphum spp., Mahanarva spp, Metcalfa pruinosa, Metopolophium dirhodum, Myndus crudus, Myzus spp., Neotoxoptera sp, Nephotettix spp., Nilaparvata spp., Nippolachnus piri Mats, Odonaspis ruthae, Oregma lanigera Zehnter, Parabemisia myricae, Paratrioza cockerelli, Parlatoria spp., Pemphigus spp., Peregrinus maidis, Perkinsiella spp, Phorodon humuli, Phylloxera spp, Planococcus spp., Pseudaulacaspis spp., Pseudococcus spp., Pseudatomoscelis seriatus, Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp., Quesada gigas, Recilia dorsalis, Rhopalosiphum spp., Saissetia spp., Scaphoideus spp., Schizaphis spp., Sitobion spp., Sogatella furcifera, Spissistilus festinus, Tarophagus Proserpina, Toxoptera spp, Trialeurodes spp, Tridiscus sporoboli, Trionymus spp, Trioza erytreae , Unaspis citri, Zygina flammigera, Zyginidia scutellaris, ; from the order Hymenoptera, for example, Acromyrmex, Arge spp, Atta spp., Cephus spp., Diprion spp., Diprionidae, Gilpinia polytoma, Hoplo- campa spp., Lasius spp., Monomorium pharaonis, Neodiprion spp., Pogonomyrmex spp, Slenopsis invicta, Solenopsis spp. and Vespa spp.; from the order / soptera, for example, Coptotermes spp, Comiternes cumulans, Incisitermes spp, Macrotermes spp, Mastotermes spp, Microtermes spp, Reticulitermes spp.; Solenopsis geminate from the order Lepidoptera, for example, Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabama argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp., Argyresthia spp, Argyrotaenia spp., Autographa spp., Bucculatrix thurberiella, Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo spp., Choristoneura spp., Chrysoteuchia topiaria, Clysia ambiguella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp., Coleophora spp., Colias lesbia, Cosmophila flava, Crambus spp, Crocidolomia binotalis, Cryptophlebia leucotreta, Cydalima perspectalis, Cydia spp., Diaphania perspectalis, Diatraea spp., Diparopsis castanea, Earias spp., Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp., Epinotia spp, Estigmene acrea, Etiella zinckinella, Eucosma spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia jaculiferia, Grapholita spp., Hedya nubiferana, Heliothis spp., Hellula undalis, Herpetogramma spp, Hyphantria cunea, Keiferia lycopersicella, Lasmopalpus lignosellus, Leucoptera scitella, Lithocollethis spp., Lobesia botrana, Loxostege bifidalis, Lymantria spp., Lyonetia spp., Malacosoma spp., Mamestra brassicae, Manduca sexta, Mythimna spp, Noctua spp, Operophtera spp., Orniodes indica, Ostrinia nubilalis, Pammene spp., Pandemis spp., Panolis flammea, Papaipema nebris, Pectinophora gossypiela, Perileucoptera coffeella, Pseudaletia unipuncta, Phthorimaea operculella, Pieris rapae, Pieris spp., Plutella xylostella, Prays spp., Pseudoplusia spp, Rachiplusia nu, Richia albicosta, Scirpophaga spp., Sesamia spp., Sparganothis spp., Spodoptera spp., Sylepta derogate, Synanthedon spp., Thaumetopoea spp., Tortrix spp., Trichoplusia ni, Tuta absoluta, and Yponomeuta spp.; from the order Mallophaga, for example, Damalinea spp. and Trichodectes spp.; from the order Orthoptera, for example, Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Neocurtilla hexadactyla, Periplaneta spp. , Scapteriscus spp, and Schistocerca spp.; from the order Psocoptera, for example, Liposcelis spp.; from the order Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp. and Xenopsylla cheopis; from the order Thysanoptera, for example, Calliothrips phaseoli, Frankliniella spp., Heliothrips spp, Hercinothrips spp., Parthenothrips spp, Scirtothrips aurantii, Sericothrips variabilis, Taeniothrips spp., Thrips spp; from the order Thysanura, for example, Lepisma saccharina. In a further aspect, the invention may also relate to a method of controlling damage to plant and parts thereof by plant parasitic nematodes (Endoparasitic-, Semiendoparasitic- and Ectoparasitic nematodes), especially plant parasitic nematodes such as root knot nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other Meloidogyne species; cyst-forming nematodes, Globodera rostochiensis and other Globodera species; Heterodera avenae, Heterodera glycines, Heterodera schachtii, Heterodera trifolii, and other Heterodera species; Seed gall nematodes, Anguina species; Stem and foliar nematodes, Aphelenchoides species; Sting nematodes, Belonolaimus longicaudatus and other Belonolaimus species; Pine nematodes, Bursaphelenchus xylophilus and other Bursaphelenchus species; Ring nematodes, Criconema species, Criconemella species, Criconemoides species, Mesocriconema species; Stem and bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci and other Ditylenchus species; Awl nematodes, Dolichodorus species; Spiral nematodes, Heliocotylenchus multicinctus and other Helicotylenchus species; Sheath and sheathoid nematodes, Hemicycliophora species and Hemicriconemoides species; Hirshmanniella species; Lance nematodes, Hoploaimus species; false rootknot nematodes, Nacobbus species; Needle nematodes, Longidorus elongatus and other Longidorus species; Pin nematodes, Pratylenchus species; Lesion nematodes, Pratylenchus neglectus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchus goodeyi and other Pratylenchus species; Burrowing nematodes, Radopholus similis and other Radopholus species; Reniform nematodes, Rotylenchus robustus, Rotylenchus reniformis and other Rotylenchus species; Scutellonema species; Stubby root nematodes, Trichodorus primitivus and other Trichodorus species, Paratrichodorus species; Stunt nematodes, Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other Tylenchorhynchus species; Citrus nematodes, Tylenchulus species; Dagger nematodes, Xiphinema species; and other plant parasitic nematode species, such as Subanguina spp., Hypsoperine spp., Macroposthonia spp., Melinius spp., Punctodera spp., and Quinisulcius spp.. The compounds of the invention may also have activity against the molluscs. Examples of which include, for example, Ampullariidae; Arion (A. ater, A. circumscriptus, A. hortensis, A. rufus); Bradybaenidae (Bradybaena fruticum); Cepaea (C. hortensis, C. Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Helicelia (H. itala, H. obvia); Helicidae Helicigona arbustorum); Helicodiscus; Helix (H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); Lymnaea; Milax (M. gagates, M. marginatus, M. sowerbyi); Opeas; Pomacea (P. canaticulata); Vallonia and Zanitoides. The active ingredients according to the invention can be used for controlling, i. e. containing or destroying, pests of the abovementioned type which occur in particular on plants, especially on useful plants and ornamentals in agriculture, in horticulture and in forests, or on organs, such as fruits, flowers, foliage, stalks, tubers or roots, of such plants, and in some cases even plant organs which are formed at a later point in time remain protected against these pests. Suitable target crops are, in particular, cereals, such as wheat, barley, rye, oats, rice, maize or sorghum; beet, such as sugar or fodder beet; fruit, for example pomaceous fruit, stone fruit or soft fruit, such as apples, pears, plums, peaches, almonds, cherries or berries, for example strawberries, raspberries or blackberries; leguminous crops, such as beans, lentils, peas or soya; oil crops, such as oilseed rape, mustard, poppies, olives, sunflowers, coconut, castor, cocoa or ground nuts; cucurbits, such as pumpkins, cucumbers or melons; fibre plants, such as cotton, flax, hemp or jute; citrus fruit, such as oranges, lemons, grapefruit or tangerines; vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes or bell peppers; Lauraceae, such as avocado, Cinnamonium or camphor; and also tobacco, nuts, coffee, eggplants, sugarcane, tea, pepper, grapevines, hops, the plantain family and latex plants. The compositions and / or methods of the present invention may be also used on any omamental and / or vegetable crops, including flowers, shrubs, broad-leaved trees and evergreens. For example the invention may be used on any of the following ornamental species: Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g. B. elatior, B. semperfiorens, B. tubéreux), Bougainvillea spp., Brachycome spp., Brassica spp. (ornamental), Calceolaria spp., Capsicum annuum, Catharanthus roseus, Canna spp., Centaurea spp., Chrysanthemum spp., Cineraria spp. (C. maritime), Coreopsis spp., Crassula coccinea, Cuphea ignea, Dahlia spp., Delphinium spp., Dicentra spectabilis, Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia spp., Geranium gnaphalium, Gerbera spp., Gomphrena globosa, Heliotropium spp., Helianthus spp., Hibiscus spp., Hortensia spp., Hydrangea spp., Hypoestes phyllostachya, Impatiens spp. (I. Walleriana), Iresines spp., Kalanchoe spp., Lantana camara, Lavatera trimestris, Leonotis leonurus, Lilium spp., Mesembryanthemum spp., Mimulus spp., Monarda spp., Nemesia spp., Tagetes spp., Dianthus spp. (carnation), Canna spp., Oxalis spp., Bellis spp., Pelargonium spp. (P. peltatum, P. Zonale), Viola spp. (pansy), Petunia spp., Phlox spp., Plecthranthus spp., Poinsettia spp., Parthenocissus spp. (P. quinquefolia, P. tricuspidata), Primula spp., Ranunculus spp., Rhododendron spp., Rosa spp. (rose), Rudbeckia spp., Saintpaulia spp., Salvia spp., Scaevola aemola, Schizanthus wisetonensis, Sedum spp., Solanum spp., Surfinia spp., Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp. and other bedding plants. For example the invention may be used on any of the following vegetable species: Allium spp. (A. sativum, A.. cepa, A. oschaninii, A. Porrum, A. ascalonicum, A. fistulosum), Anthriscus cerefolium, Apium graveolus, Asparagus officinalis, Beta vulgarus, Brassica spp. (B. Oleracea, B. Pekinensis, B. rapa), Capsicum annuum, Cicer anetinum, Cichorium endivia, Cichorum spp. (C. intybus, C. endivia), Citrillus fanatus, Cucumis spp. (C. sativus, C. melo), Cucurbita spp. (C. pepo, C. maxima), Cyanara spp. (C. scolymus, C. cardunculus), Daucus carota, Foeniculum vulgare, Hypericum spp., Lactuca sativa, Lycopersicon spp. (L. esculentum, L. lycopersicum), Mentha spp., Ocimum basilicurn, Petroselinum crispum, Phaseolus spp. (P. vulgaris, P. coccineus), Pisum sativum, Raphanus sativus, Rheum rhaponticum, Rosemarinus spp., Salvia spp., Scorzonera hispanica, Solanum melongena, Spinacea oleracea, Valerianella spp. (V. locusta, V. eriocarpa) and Vicia faba. Preferred omamental species include African violet, Begonia, Dahlia, Gerbera, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia, Aster, Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia, Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Salvia, Hortensia, rosemary, sage, St. Johnswort, mint, sweet pepper, tomato and cucumber. The active ingredients according to the invention are especially suitable for controlling Aphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostella and Spodoptera littoralis in cotton, vegetable, maize, rice and soya crops. The active ingredients according to the invention are further especially suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis (preferably in rice). The compounds of formula | are particularly suitable for control of a pest of the order Hemiptera, for example, one or more of the species Bemisia tabaci , Aphis craccivora, Myzus persicae, Rhopalosiphum Padi, Nilaparvata lugens, and Euschistus heros (preferably in vegetables, soybeans, and sugarcane); a pest of the order Lepidoptera, for example, one or more of the species Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includes, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta (preferably in vegetables and corn); a pest of the order Thysanoptera, such as the family Thripidae, for example, one or more of Thrips tabaci and Frankliniella occidentalis (preferably in vegetables); and soil pests (such as of the order Coleoptera), for example, the species Diabrotica balteata, Agriotes spp. and Leptinotarsa decemlineata (preferably in vegetables and corn). The term "crops" is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus. Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, for example insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as O-endotoxins, e.g. Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1, Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases. In the context of the present invention there are to be understood by O-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1, Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02 / 15701). Truncated toxins, for example a truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03 / 018810). Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93 / 07278, WO 95 / 34656, EP-A-0 427 529, EP-A-451 878 and WO 03 / 052073. The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Cryl-type deoxyribonucleic acids and their preparation are known, for example, from WO 95 / 34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90 / 13651. The toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and moths (Lepidoptera). Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard® (maize variety that expresses a Cry1Ab toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a Cry1Ab and a Cry3Bb1 toxin); Starlink® (maize variety that expresses a Cry8C toxin); Herculex I® (maize variety that expresses a Cry1Fa2 toxin and the enzyme phosphinothricine N-acetyitransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a Cry1Ac toxin); Bollgard I® (cotton variety that expresses a Cry1Ac toxin); Bollgard 1i® (cotton variety that expresses a Cry1Ac and a Cry2Ab toxin); VipCot® (cotton variety that expresses a Vip3A and a Cry1Ab toxin); NewLeaf® (potato variety that expresses a Cry3A toxin); NatureGard®, Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait) and Protecta®. Further examples of such transgenic crops are: 1. Bt11 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C / FR / 96 / 05 / 10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium. 2. Bt176 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C / FR / 96 / 05 / 10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a Cry1Ab toxin. Bt176 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium. 3. MIR604 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C / FR / 96 / 05 / 10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G- protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03 / 018810. 4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C / DE / 02 / 9. MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects. 5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C / ES / 96 / 02. 6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160 Brussels, Belgium, registration number C / NL / 00 / 10. Genetically modified maize for the expression of the protein Cry1F for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium. 7. NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C / GB / 02 / M3 / 03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603 x MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a Cry1Ab toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer. Transgenic crops of insect-resistant plants are also described in BATS (Zentrum fiir Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003, http: / / bats.ch). The term "crops" is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95 / 33818 and EP-A-0 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Crops may also be modified for enhanced resistance to fungal (for example Fusarium, Anthracnose, or Phytophthora), bacterial (for example Pseudomonas) or viral (for example potato leafroll virus, tomato spotted wilt virus, cucumber mosaic virus) pathogens. Crops also include those that have enhanced resistance to nematodes, such as the soybean cyst nematode. Crops that are tolerance to abiotic stress include those that have enhanced tolerance to drought, high salt, high temperature, chill, frost, or light radiation, for example through expression of NF-YB or other proteins known in the art. Antipathogenic substances which can be expressed by such transgenic plants include, for example, jon channel blockers, such as blockers for sodium and calcium channels, for example the viral KP1, KP4 or KP8 toxins; stilbene synthases; bibenzyl synthases; chitinases; glucanases; the so-called "pathogenesis-related proteins" (PRPs; see e.g. EP-A-0 392 225); antipathogenic substances produced by microorganisms, for example peptide antibiotics or heterocyclic antibiotics (see e.g. WO 95 / 33818) or protein or polypeptide factors involved in plant pathogen defence (so-called "plant disease resistance genes", as described in WO 03 / 000806). Further areas of use of the compositions according to the invention are the protection of stored goods and store rooms and the protection of raw materials, such as wood, textiles, floor coverings or buildings, and also in the hygiene sector, especially the protection of humans, domestic animals and productive livestock against pests of the mentioned type. The present invention provides a compound of the first aspect for use in therapy. The present invention provides a compound of the first aspect, for use in controlling parasites in or on an animal. The present invention further provides a compound of the first aspect, for use in controlling ectoparasites on an animal. The present invention further provides a compound of the first aspect, for use in preventing and / or treating diseases transmitted by ectoparasites. The present invention provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling parasites in or on an animal. The present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling ectoparasites on an animal. The present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for preventing and / or treating diseases transmitted by ectoparasites. The present invention provides the use of a compound of the first aspect, in controlling parasites in or on an animal. The present invention further provides the use of a compound of the first aspect , in controlling ectoparasites on an animal. The term "controlling" when used in context of parasites in or on an animal refers to reducing the number of pests or parasites, eliminating pests or parasites and / or preventing further pest or parasite infestation. The term "treating" when used used in context of parasites in or on an animal refers to restraining, slowing, stopping or reversing the progression or severity of an existing symptom or disease. The term "preventing" when used used in context of parasites in or on an animal refers to the avoidance of a symptom or disease developing in the animal. The term "animal" when used used in context of parasites in or on an animal may refer to a mammal and a non-mammal, such as a bird or fish. In the case of a mammal, it may be a human or non-human mammal. Non-human mammals include, but are not limited to, livestock animals and companion animals. Livestock animals include, but are not limited to, cattle, camellids, pigs, sheep, goats and horses. Companion animals include, but are not limited to, dogs, cats and rabbits. A “parasite” is a pest which lives in or on the host animal and benefits by deriving nutrients at the host animal's expense. An "endoparasite” is a parasite which lives in the host animal. An "ectoparasite” is a parasite which lives on the host animal. Ectoparasites include, but are not limited to, acari, insects and crustaceans (e.g. sea lice). The Acari (or Acarina) sub-class comprises ticks and mites. Ticks include, but are not limited to, members of the following genera: Rhipicaphalus, for example, Rhipicaphalus (Boophilus) microplus and Rhipicephalus sanguineus; Amblyomrna; Dermacentor, Haemaphysalis; Hyalomma; Ixodes; Rhipicentor,; Margaropus; Argas; Otobius; and Omithodoros. Mites include, but are not limited to, members of the following genera: Chorioptes, for example Chorioptes bovis; Psoroptes, for example Psoroptes ovis; Cheyletiella; Dermanyssus; for example Dermanyssus gallinae; Ortnithonyssus; Demodex, for example Demodex canis; Sarcoptes, for example Sarcoptes scabiei; and Psorergates. Insects include, but are not limited to, members of the orders: Siphonaptera, Diptera, Phthiraptera, Lepidoptera, Coleoptera and Homoptera. Members of the Siphonaptera order include, but are not limited to, Ctenocephalides felis and Ctenocephatides canis. Members of the Diptera order include, but are not limited to, Musca spp.; bot fly, for example Gasterophilus intestinalis and Oestrus ovis; biting flies; horse flies, for example Haematopota spp. and Tabunus spp.; haematobia, for example haematobia irritans; Stomoxys; Lucilia; midges; and mosquitoes. Members of the Phthiraptera class include, but are not limited to, blood sucking lice and chewing lice, for example Bovicola Ovis and Bovicola Bovis. The term "effective amount" when used used in context of parasites in or on an animal refers to the amount or dose of the compound of the invention, or a salt thereof, which, upon single or multiple dose administration to the animal, provides the desired effect in or on the animal. The effective amount can be readily determined by the attending diagnostician, as one skilled in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered by the attending diagnostician, including, but not limited to: the species of mammal; its size, age, and general health; the parasite to be controlled and the degree of infestation; the specific disease or disorder involved; the degree of involvement or the severity of the disease or disorder; the response of the individual; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; the use of concomitant medication; and other relevant circumstances. The compounds of the invention may be administered to the animal by any route which has the desired effect including, but not limited to topically, orally, parenterally’ and subcutaneously. Topical administration is preferred. Formulations suitable for topical administration include, for example, solutions, emulsions and suspensions and may take the form of a pour-on, spot-on, spray-on, spray race or dip. In the alternative, the compounds of the invention may be administered by means of an ear tag or collar. Salt forms of the compounds of the invention include both pharmaceutically acceptable salts and veterinary acceptable salts, which can be different to agrochemically acceptable salts. Pharmaceutically and veterinary acceptable salts and common methodology for preparing them are well known in the art. See, for example, Gould, P.L., "Salt selection for basic drugs", International Journal of Pharmaceutics, 33: 201 -217 (1986); Bastin, R.J., ef al. "Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities", Organic Process Research and Development, 4: 427-435 (2000); and Berge, S.M., et al., "Pharmaceutical Salts", Jounal of Pharmaceutical Sciences, 66: 1-19, (1977). One skilled in the art of synthesis will appreciate that the compounds of the invention are readily converted to and may be isolated as a salt, such as a hydrochloride salt, using techniques and conditions well known to one of ordinary skill in the art. In addition, one skilled in the art of synthesis will appreciate that the compounds of the invention are readily converted to and may be isolated as the corresponding free base from the corresponding salt. The present invention also provides a method for controlling pests (such as mosquitoes and other disease vectors; see also http: / mwww.who.int / malaria / vector_controliirs / en / ). In one embodiment, the method for controlling pests comprises applying the compositions of the invention to the target pests, to their locus or to a surface or substrate by brushing, rolling, spraying, spreading or dipping. By way of example, an IRS (indoor residual spraying) application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention. In another embodiment, it is contemplated to apply such compositions to a substrate such as non-woven or a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents. In one embodiment, the method for controlling such pests comprises applying a pesticidally effective amount of the compositions of the invention to the target pests, to their locus, or to a surface or substrate so as to provide effective residual pesticidal activity on the surface or substrate. Such application may be made by brushing, rolling, spraying, spreading or dipping the pesticidal composition of the invention. By way of example, an IRS application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention so as to provide effective residual pesticidal activity on the surface. In another embodiment, it is contemplated to apply such compositions for residual control of pests on a substrate such as a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents. Substrates including non-woven, fabrics or netting to be treated may be made of natural fibres such as cotton, raffia, jute, flax, sisal, hessian, or wool, or synthetic fibres such as polyamide, polyester, polypropylene, polyacrylonitrile or the like. The polyesters are particularly suitable. The methods of textile treatment are known, e.g. WO 2008 / 151984, WO 2003 / 034823, US 5631072, WO 2005 / 64072, WO2006 / 128870, EP 1724392, WO 2005113886 or WO 2007 / 090739. Further areas of use of the compositions according to the invention are the field of tree injection / trunk treatment for all ornamental trees as well all sort of fruit and nut trees. In the field of tree injection / trunk treatment, the compounds according to the present invention are especially suitable against wood-boring insects from the order Lepidoptera as mentioned above and from the order Coleoptera, especially against woodborers listed in the following tables A and B: Table A. Examples of exotic woodborers of economic importance. Family Species Host or Crop Infested Buprestidae Agrilus planipennis Ash Cerambycidae Anoplura glabripennis Hardwoods Xylosandrus crassiusculus Hardwoods | Scolytidae X. mutilatus Hardwoods Tomicus piniperda Conifers Table B. Examples of native woodborers of economic importance. Chrysobothris femorata | Buprestidae Texania campestris [Family Species Host or Crop Infested Agrilus anxius Birch Agrilus politus Willow, Maple Agrilus sayi Bayberry, Sweetfern Agrilus vittaticolllis Apple, Pear, Cranberry, Serviceberry, Hawthorn (Chrysabotiris femorata Apple, Apricot, Beech, Boxelder, Cherry, Chestnut, Currant, Em, | Buprestidae Hawthorn, Hackberry, Hickory, Horsechestnut, Linden, Maple, Mountain-ash, Oak, Pecan, Pear, Peach, Persimmon, Plum, Poplar, Quince, Redbud, Serviceberry, Sycamore, Walnut, Willow [Texania campesis Basswood, Beech, Maple, Oak, Sycamore, Willow, Yellow-poplar Family Species Goes pulverulentus Goes tigrinus Neoclytus acuminatus | Cerambycidae | Neoptychodes trilineatus Oberea ocellata Oberea tripunctata Oncideres cingulata Saperda calcarata Strophiona nitens Corthylus columbianus | Scolytidae Dendroctonus frontalis Dryocoetes betulae Family Species 'Monarthrum fasciatum Phloeotribus liminaris Paranthrene simulans Sannina uroceriformis Synanthedon exitiosa Synanthedon pictipes | Sesiidae Synanthedon rubrofascia Synanthedon scitula Vitacea polistiformis The present invention may be also used to control any insect pests that may be present in turfgrass, including for example beetles, caterpillars, fire ants, ground pearls, millipedes, sow bugs, mites, mole crickets, scales, mealybugs, ticks, spittlebugs, southern chinch bugs and white grubs. The present invention may be used to control insect pests at various stages of their life cycle, including eggs, larvae, nymphs and adults. In particular, the present invention may be used to control insect pests that feed on the roots of turfgrass including white grubs (such as Cyclocephala spp. (e.g. masked chafer, C. lurida), Rhizotrogus spp. (e.g. European chafer, R. majalis), Cotinus spp. (e.g. Green June beetle, C. nitida), Popillia spp. (e.g. Japanese beetle, P. japonica), Phyllophaga spp. (e.g. May / June beetle), Ataenius spp. (e.g. Black turfgrass ataenius, A. spretulus), Maladera spp. (e.g. Asiatic garden beetle, M. castanea) and Tomarus spp.), ground pearls (Margarodes spp.), mole crickets (tawny, southern, and short-winged; Scapteriscus spp., Gryllotalpa africana) and leatherjackets (European crane fly, Tipula spp.). The present invention may also be used to control insect pests of turfgrass that are thatch dwelling, including armyworms (such as fall armyworm Spodoptera frugiperda, and common armyworm Pseudaletia unipuncta), cutworms, billbugs (Sphenophorus spp., such as S. venatus verstitus and S. parvulus), and sod webworms (such as Crambus spp. and the tropical sod webworm, Herpetogramma phaeopteralis). The present invention may also be used to control insect pests of turfgrass that live above the ground and feed on the turfgrass leaves, including chinch bugs (such as southern chinch bugs, Blissus insularis), Bermudagrass mite (Eriophyes cynodoniensis), rhodesgrass mealybug (Antonina graminis), two-lined spittlebug (Propsapia bicincta), leafhoppers, cutworms (Noctuidae family), and greenbugs. The present invention may also be used to control other pests of turfgrass such as red imported fire ants (Solenopsis invicta) that create ant mounds in turf. In the hygiene sector, the compositions according to the invention are active against ectoparasites such as hard ticks, soft ticks, mange mites, harvest mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice and fleas. Examples of such parasites are: Of the order Anoplurida: Haematopinus spp., Linognathus spp., Pediculus spp. and Phtirus spp., Solenopotes spp.. Of the order Mallophagida: Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes spp. and Felicola spp.. Of the order Diptera and the suborders Nematocerina and Brachycerina, for example Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohifahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp. and Melophagus spp.. Of the order Siphonapterida, for example Pulex spp., Ctenocephalides spp., Xenopsylla spp., Ceratophyllus spp.. Of the order Heteropterida, for example Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp.. Of the order Blattarida, for example Blatta orientalis, Periplaneta americana, Blattelagermanica and Supella spp.. Of the subclass Acaria (Acarida) and the orders Meta- and Meso-stigmata, for example Argas spp., Omithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp., Pneumonyssus spp., Stemostoma spp. and Varroa spp.. Of the orders Actinedida (Prostigmata) and Acaridida (Astigmata), for example Acarapis spp., Cheyletiella spp., Omithocheyletia spp., Myobia spp., Psorergatesspp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp. and Laminosioptes spp.. The compositions according to the invention are also suitable for protecting against insect infestation in the case of materials such as wood, textiles, plastics, adhesives, glues, paints, paper and card, leather, floor coverings and buildings. The compositions according to the invention can be used, for example, against the following pests: beetles such as Hylotrupes bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, Emobius mollis, Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus planicoliis, Lyctus linearis, Lyctus pubescens, Trogoxylon aequale, Minthesrugicollis, Xyleborus spec. Tryptodendron spec., Apate monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon spec. and Dinoderus minutus, and also hymenopterans such as Sirex juvencus, Urocerus gigas, Urocerus gigas taignus and Urocerus augur, and termites such as Kalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola, Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermes lucifugus, Mastotermes darwiniensis, Zootermopsis nevadensis and Coptotermes formosanus, and bristletails such as Lepisma saccharina. The compounds of formulae |, and I'a, or salts thereof, are especially suitable for controlling one or more pests selected from the family: Noctuidae, Pluteliidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae. In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables D-1 to D-66 and Table P”) controls one or more of pests selected from the family: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae. The compounds of formulae |, and I'a, or salts thereof, are especially suitable for controlling one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp. In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables D-1 to D-66 and Table P") controls one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp. The compounds of formulae |, and I'a, or salts thereof, are especially suitable for controlling one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum padi, and Chilo suppressalis. In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables D-1 to D-66 and Table P”) controls one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis, such as Spodoptera littoralis + TX, Plutella xylostella + TX; Frankliniella occidentalis + TX, Thrips tabaci + TX, Euschistus heros + TX, Cydia pomonella + TX, Nilaparvata lugens + TX, Myzus persicae + TX, Chrysodeixis includens + TX, Aphis craccivora + TX, Diabrotica balteata + TX, Rhopalosiphum Padi + TX, and Chilo suppressalis + TX. In an embodiment, of each aspect, one compound from Tables D-1 to D-66 and Table P is suitable for controlling Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis in cotton, vegetable, maize, cereal, rice and soya crops. In an embodiment, one compound from Tables D-1 to D-66 and Table P is suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis (preferably in rice). Compounds according to the invention may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against insects or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability). In particular, it has been surprisingly found that certain compounds of formula | may show an advantageous safety profile with respect to non-target arthropods, in particular pollinators such as honey bees, solitary bees, and bumble bees. Most particularly, Apis mellifera. The compounds according to the invention can be used as pesticidal agents in unmodified form, but they are generally formulated into compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances. The formulations can be in various physical forms, e.g. in the form of dusting powders, gels, wettable powders, water-dispersible granules, water- dispersible tablets, effervescent pellets, emulsifiable concentrates, microemulsifiable concentrates, oil- in-water emulsions, oil-flowables, aqueous dispersions, oily dispersions, suspo-emulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water- miscible organic solvent as carrier), impregnated polymer films or in other forms known e.g. from the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations can either be used directly or diluted prior to use. The dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents. The formulations can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof. The active ingredients can also be contained in very fine microcapsules. Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release). Microcapsules usually have a diameter of from 0.1 to 500 microns. They contain active ingredients in an amount of about from 25 to 95 % by weight of the capsule weight. The active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. The encapsulating membranes can comprise, for example, natural or synthetic rubbers, cellulose, styrene / butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated. The formulation adjuvants that are suitable for the preparation of the compositions according to the invention are known per se. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p- diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4- dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2- heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxy- propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and alcohols of higher molecular weight, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2- pyrrolidone and the like. Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyliite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances. A large number of surface-active substances can advantageously be used in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier prior to use. Surface- active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol / alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol / alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2- ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di- alkylphosphate esters; and also further substances described e.g. in McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood New Jersey (1981). Further adjuvants that can be used in pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and liquid and solid fertilisers. The compositions according to the invention can include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive in the composition according to the invention is generally from 0.01 to 10 %, based on the mixture to be applied. For example, the oil additive can be added to a spray tank in the desired concentration after a spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. Preferred oil additives comprise alkyl esters of Cs-Cz22 fatty acids, especially the methyl derivatives of C12-C1s fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively). Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10* Edition, Southern Illinois University, 2010. The inventive compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, of compounds of the present invention and from 1 to 99.9 % by weight of a formula- tion adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance. Whereas commercial products may preferably be formulated as concentrates, the end user will normally employ dilute formulations. The rates of application vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. As a general guideline compounds may be applied at a rate of from 1 to 2000 I / ha, especially from 10 to 1000 l / ha. Preferred formulations can have the following compositions (weight %): Emulsifiable concentrates: active ingredient: 1 to 95 %, preferably 60 to 90 % surface-active agent: 1 to 30 %, preferably 5 to 20 % liquid carrier: 1 to 80 %, preferably 1 to 35 % Dusts: active ingredient: 0.1to 10 %, preferably 0.1 to 5 % solid carrier: 99.9 to 90 %, preferably 99.9 to 99 % Suspension concentrates: active ingredient: 5to 75 %, preferably 10 to 50 % water: 94 to 24 %, preferably 88 to 30 % surface-active agent: 1 to 40 %, preferably 2 to 30 % Wettable powders: active ingredient: 0.5 to 90 %, preferably 1 to 80 % surface-active agent: 0.510 20 %, preferably 1 to 15 % solid carrier: 5 to 95 %, preferably 15 to 90 % Granules: active ingredient: 0.1 to 30 %, preferably 0.1 to 15 % solid carrier: 99.5 to 70 %, preferably 97 to 85 % The following Examples further illustrate, but do not limit, the invention. 59% a) b) ©) 25% 50% | 75% 5% 5% |- 3% “5% 6% 10% 2% Wettable powders a) b) c) active ingredients 25% 50 % 75% sodium lignosulfonate 5% 5% |- sodium lauryl sulfate 3% “5% sodium diisobutyinaphthalenesulfonate o% [10% phenol polyethylene glycol ether (7-8 mol of ethylene 2% oxide) highly dispersed silicic acid 5% 10 % 10 % Kaolin 27% The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration. Powders for dry seed treatment a) b) ©) active ingredients 25% 50 % 75% light mineral oil 5% “5% 5% highly dispersed silicic acid 5% 5% [- Kaolin 65 % 40 % Talcum Te Tow Ie 20% The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment. [ Emulsifiable concentrate active ingredients 10% octylphenol polyethylene glycol ether (4-5 mol of ethylene 3% oxide) calcium dodecylbenzenesulfonate 3% castor oil polyglycol ether (35 mol of ethylene oxide) 4% Cyclohexanone 30 % xylene mixture 50 % Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water. b) ) 5% 7% TT a) 5% 95 % Dusts a) b) ©) Active ingredients 5% Ce NES Talcum 95% - T= Kaolin 1 94% - mineral filler - 1 Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed. TEE 2% Extruder granules Active ingredients TEE sodium lignosulfonate “2% carboxymethylcellulose 1% Kaolin 82 % The combination is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air. 39% Coated granules Active ingredients “8% polyethylene glycol (mol. wt. 200) “3% Kaolin ~~ 89 % The finely ground combination is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner. Suspension concentrate active ingredients 40 % propylene glycol 10 % nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6% Sodium lignosulfonate 10 % carboxymethylcellulose 1% silicone oil (in the form of a 75 % emulsion in water) 1% Water 332% The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion. Flowable concentrate for seed treatment active ingredients 40 % propylene glycol 5% copolymer butanol PO / EO 2% Tristyrenephenole with 10-20 moles EQ 2% 1,2-benzisothiazolin-3-one (in the form of a 20% solution in water) 0.5% monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75 % emulsion in water) 02% Water 45.3 % The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion. Slow Release Capsule Suspension 28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate / polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed. The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns. The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose. Formulation types include an emulsion concentrate (EC), a suspension concentrate (SC), a suspo- emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP), a soluble granule (SG) or any technically feasible formulation in combination with agriculturally acceptable adjuvants. Preparatory Examples: LCMS Methods: Method 1: Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions, Capillary: 3.00 kV, Cone range: 30 V, Extractor: 2.00 V, Source Temperature: 150°C, Desolvation Temperature: 350°C, Cone Gas Flow: 50 I / h, Desolvation Gas Flow: 650 l / h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment , diode-array detector and ELSD detector. Column: Waters UPLC HSS T3, 1.8 um, 30 x 2.1 mm, Temp: 60 °C, DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A = water + 5% MeOH + 0.05 % HCOOH, B = Acetonitrile + 0.05 % HCOOH, gradient: 10-100% B in 1.2 min; Flow (ml / min) 0.85. Method 2: Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source(Polarity: positive and negative ions, Capillary: 3.00 kV, Cone range: 41 V, Extractor: 2.00 V, Source Temperature: 150°C, Desolvation Temperature: 5000°C, Cone Gas Flow: 50 I / h, Desolvation Gas Flow: 1000 I / h, Mass range: 110 to 800 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment , diode-array detector and ELSD detector. Column: Waters UPLC HSS T3, 1.8 um, 30 x 2.1 mm, Temp: 40 °C, PDA Wavelength range (nm): 200 to 400, Solvent Gradient: A = water + 5% Acetonitrile + 0.1 % HCOOH, B = Acetonitrile + 0.05 % HCOOH, gradient: 10-100% B in 1.3 min; Flow (ml / min) 0.6. Method 3: Spectra were recorded on a Mass Spectrometer from Waters Corporation (SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions, Capillary: 0.8-3.00 kV, Cone: 5-30 V, Source Temperature: 120-150°C, Desolvation Temperature: 350-600°C, Cone Gas Flow: 50-150 I / h, Desolvation Gas Flow: 650-1000 I / h, Mass range: 50 to 900 Da and an Acquity UPLC from Waters Corporation: Binary pump, heated column compartment , diode-array detector and ELSD. Column: Waters UPLC HSS T3, 1.8 pm, 30 x 2.1 mm, Temp: 60 °C, DAD Wavelength range (nm): 210 to 400, Runtime: 1.5 min; Solvents: A = water + 5% MeOH + 0.05 % HCOOH, B= Acetonitrile + 0.05 % HCOOH; Flow (ml / min) 0.85, Gradient: 10% B isocratic for 0.2 min, then 10-100% B in 1.0 min, 100% B isocratic for 0.2min, 100-10% B in 0.05min, 10% B isocratic for 0.05 min. Method 4: Spectra were recorded on a Mass Spectrometer from Waters Corporation (SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions, Capillary: 3.00 kV, Cone: 41 V, Source Temperature: 150°C, Desolvation Temperature: 500 °C, Cone Gas Flow: 50 I / h, Desolvation Gas Flow: 1000 I / h, Mass range: 110 to 800 Da and an Acquity UPLC from Waters Corporation: Binary pump, heated column compartment , diode-array detector and ELSD. Column: Waters UPLC HSS T3, 1.8 ym, 30 x 2.1 mm, Temp: 40 °C, DAD Wavelength range (nm): 200 to 400, Runtime: 1.6 min; Solvents: A = water + 5% Acetonitrile + 0.1 % HCOOH, B= Acetonitrile + 0.05 % HCOOH; Flow (ml / min) 0.6, Gradient: 10-50% B in 0.2 min, then 50-100% B in 0.5 min, 100% B isocratic for 0.6 min, 100-10% B in 0.05min, 100% to 10% Bin 0.1 min, then 10% B isocratic for 0.2 min. Method 5: Spectra were recorded on a Mass Spectrometer from Agilent Technologies (SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions, Capillary: 4.00 kV, Fragmentor: 100 V, Gas Temperature (C): 350, Gas Flow: 11 l / min, Mass range: 110 to 1000 Da and an Agilent HPLC from Agilent Technologies: Column: KINETEX EVO C18, 2.6 um, 50 x 4.6 mm, Temp: 40 °C, DAD Wavelength range (nm): 210 to 400, Runtime: 2.5 min; Solvents: A = water + 5% Acetonitrile + 0.1 % HCOOH, B= Acetonitrile + 0.1 % HCOOH; Flow (ml / min) 1.8, Gradient: 10-100% B in 0.9 min, 100% B isocratic for 0.9 min, 100-10% B in 0.4 min, 10% B isocratic for 0.2 min. Example 1: Preparation of N-[(18)-1-(2-pyrimidin-2-yl-1,2 4-triazol-3-yl)ethy|]-6,8- bis(trifluoromethyl)quinolin-4-amine (compound P.5) = NN No N = H NN = NPY "y “ore CFa CFs (P.5) Step A: Preparation of 5-[[2 4-bis(trifluoromethyhanilinojmethylene]-2,2-dimethyl-1,3-dioxane-4.6- dione (intermediate I-1 CF3 1-1) 2,2-dimethyl-1,3-dioxane-4,6-dione (3.46 g, 24 mmol, 1.2 equiv.) and trimethoxymethane (11 mL, 96 mmol, 4.8 equiv.) are heated to reflux for 90 mins. Next, 2,4-bis(trifluoromethyl)aniline (4.72 g, 20 mmol, 1 equiv.) was added at the same temperature and the solution stirred for 50 minutes. Stirring and heating were turned off and a solid started precipitating. The solid was collected at room temperature and washed with cyclohexane and air dried. A second crop of solid can be collected from the filtrate and washed with cyclohexane. The product I-1 is obtained as an off-white solid (6.27 g, 82%). H NMR (400 MHz, CDCls) 6 ppm: 1.80 (s, 6 H), 7.64 (d, J=8.80 Hz, 1 H), 7.96 (d, J=8.44 Hz, 1 H), 7.98-8.03 (m, 1 H), 8.67 (d, J=13.20 Hz, 1 H), 11.87 (br d, J=12.84 Hz, 1 H). Step B: Preparation of 6 8-bis(trifluoromethyl)-1H-qguinolin-4-one (intermediate 1-2) CF3 (1-2) 5-[[2,4-bis(trifluoromethyl)anilino]methylene]-2,2-dimethyl-1,3-dioxane-4,6-dione (I-1, 3.12 g, 8.14 mmol) is added to diphenyl ether (15 mL) while refluxing. The mixture was stirred at reflux for 30 minutes, then allowed to cool to room temperature. Reaction was diluted with cyclohexane (20 mL), then the precipitate was filtered and washed with copious amounts of cyclohexane. The desired product was obtained as a light-brown powder (1.63 g, 71%). "H NMR (400 MHz, DMSO-de) 5 ppm: 6.33 (brs, 1 H), 7.97 (brs, 1 H), 8.33 (s, 1 H), 8.66 (brs, 1 H), 11.57 (brs, 1 H). LC-MS (method 3): retention time 0.86 min, m / z 282 [M+H*]. Step C: Preparation of 4-chloro-6,8-bis(trifluoromethyl)quinoline (intermediate |-3 CF3 (1-3) To a flask containing 6,8-bis(trifluoromethyl)-1H-quinolin-4-one (I-3, 2.76 g, 9.81 mmol) was added phosphoryl trichloride (3 mL, 31.5 mmol, 3.21 equiv.) and the mixture was stirred at 100 °C for 15 minutes, then allowed to cool to room temperature, then placed in an ice bath. The reaction was quenched with water and aqueous ammonia is added till the pH reached 8-9. The mixture was then extracted three times with dichloromethane (3 x 100 mL) and concentrated under reduced pressure to provide desired product as a light brown powder (2.5 g, 8.3 mmol, 85%). "H NMR (400 MHz, CDCls) 8 ppm: 7.75 (d, J=4.77 Hz, 1 H), 8.34 (s, 1 H), 8.82 (s, 1 H), 9.08 (d, J=4.77 Hz, 1 H). LC-MS (method 3): retention time 1.18 min, m / z 300 [M+H*]. Step D: Preparation of (25)-2-[[6,8-bis(trifluoromethyl)-4-quinolyllamino]propanamide (intermediate I- 4) ¥ | NH2 N “vy CF» CF (1-4) To a solution of 4-chloro-6,8-bis(trifluoromethyl)quinoline (1-3, 1.51 g, 5.04 mmol) in N,N- dimethylformamide (50 mL) was added (2S)-2-aminopropanamide hydrochloride (3.24 g, 25.2 mmol, 5.00 equiv.) and potassium carbonate (4.88 g, 35.3 mmol, 7 equiv.). The reaction mixture was heated to 100 °C overnight. The reaction was cooled, diluted with water and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded the desired product as a brown solid (541 mg, 31% yield). H NMR (400 MHz, DMSO-d) 6 ppm: 1.49 - 1.58 (m, 3 H), 4.09 - 4.19 (m, 1 H), 6.49 - 6.55 (m, 1 H), 7.43-7.22(m, 1 H), 7.63- 7.71 (m, 1 H), 7.83 - 7.90 (m, 1 H), 8.17 - 8.24 (m, 1 H), 8.60 - 8.66 (m, 1 H), 9.23 -9.29 (m, 1 H). LC-MS (method 3): retention time 0.75 min, m / z 352 [M+H"]. Step E: Preparation of (28)-2-[[6,8-bis(trifluoromethyl)-4-quinolyllamino]-N- dimethylaminomethylene)propanamide (compound |-5; OS MYL FiC NAN Ho CF, CF, (1-5) To a solution of (28)-2-[[6,8-bis(trifluoromethyl)-4-quinolyllamino]propanamide (1-4, 0.74 g, 2.1 mmol) in 2-methyltetrahydrofuran (21 mL) was added 1,1-dimethoxy-N,N-dimethyl-methanamine (0.56 mL, 4.2 mmol, 2 equiv.) and the reaction mixture was stirred at 50 °C for 30 minutes. The reaction was cooled and concentrated under reduced pressure to provide (2S)-2-[[6,8-bis(trifluoromethyl)-4- quinolylJamino]-N-(dimethylaminomethylene)propanamide (1-5) as a brown solid (755 mg, 80%). H NMR (400 MHz, DMSO-de) 8 ppm: 1.57 (d, J=6.97 Hz, 3 H), 2.98 - 3.09 (m, 3 H), 3.10 - 3.19 (m, 3 H), 4.22 - 4.37 (m, 1 H), 6.45 - 6.55 (m, 1 H), 7.83 - 7.94 (m, 1 H), 8.17 - 8.25 (m, 1 H), 8.43 - 8.52 (m, 1H), 8.52-8.60 (m, 1 H), 9.20 - 9.31 (m, 1 H). Step F: Preparation of N-[(18)-1-(2-pyrimidin-2-yl-1,2 4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quinolin-4-amine (compound P.5) = NH N 11 SN H WN A NPY "y “rhe CF3 CF3 (P.5 (28)-2-[[6,8-bis(trifluoromethyl)-4-quinolylJamino]-N-(dimethylaminomethylene)propenamide (I-5 prepared above, 755 mg, 1.86 mmol, 1 equiv.) was dissolved in 2-methyltetrahydrofuran (7.4 mL). Next, pyrimidin-2-ylhydrazine hydrochloride (0.49 g, 3.35 mmol) and acetic acid (4.65 mL) were added and the reaction was stirred at 80°C for 1 hour. The reaction was cooled, diluted with ethyl acetate and extracted with water. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded the desired product (P.5) as a light brown solid (631.5 mg, 75% yield). 'H NMR (400 MHz, DMSO-de) 8 ppm: 1.76 (d, J=6.97 Hz, 3 H), 5.96 (quin, J=7.06 Hz, 1 H), 6.60 (d, J=5.87 Hz, 1 H), 7.51 - 7.62 (m, 1 H), 8.15 - 8.22 (m, 2 H), 8.26 (d, J=7.34 Hz, 1 H), 8.55 (d, J=5.50 Hz, 1 H), 8.92 (d, J=5.14 Hz, 2 H), 9.14 (s, 1 H). LC-MS (method 3): retention time 0.88 min, m / z 455 [M+H"]. Example 2: Preparation of N-[1-(2-pyrimidin-2-yl-1,2.4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quinazolin-4-amine (compound P.16) = aN N 1 SN H LN ~ NN Ns FsC N Or CFs CF3 (P.16) Step A: Preparation of 2-iodo-4 8-bis(trifluoromethyl aniline (intermediate 1-6) CF; (1-6) 2,4-Bis(trifluoromethyl)aniline (CAS No. 367-71-5, 1.50 g, 6.2 mmol) was dissolved in 1,1,1,3,3,3- hexafluoro-2-propanol and the solution cooled to 0 °C. N-iodosuccinimide (1.47 g, 8.2 mmol, 1 equiv.) was added and the reaction stirred at 0 °C for 1 h and then at room temperature overnight. The reaction was concentrated under reduced pressure and the crude material purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to obtain product (1-6) as a light pink crystalline solid (2.09 g, 95%). TH NMR (400 MHz, CDCls) 5 ppm: 5.08 (br s, 2 H), 7.70 - 7.74 (m, 1 H), 8.06 (d, J=1.47 Hz, 1 H). Step B: Preparation of 2-amino-3,5-bis(trifluoromethyl)benzonitrile (intermediate 1-7' CFs (1-7) A sealed tube was charged with 2-iodo-4,6-bis(trifluoromethyl)aniline (1-6, 1.00 g, 2.82 mmol), N,N- dimethylformamide (5.63 mL) and copper(l) cyanide (0.31 g, 3.38 mmol, 1.2 equiv.). The mixture was stirred at 100 °C overnight. The mixture was cooled, filtered through celite and extracted twice with MTBE (2 x 20 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under vacuum. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded the desired product (I-7) as a brown solid (567 mg, 79%). H NMR (400 MHz, CDCls) § ppm: 5.33 (br s, 2 H), 7.83 - 7.90 (m, 2 H). 19F NMR (377 MHz, CDCls) 8 ppm: -63.94 (s, 1 F), -62.19 (5, 1 F). LC-MS (method 3): retention time 1.01 min, m / z 253 [M-H]. Step C: Preparation of 6,8-bis(trifluoromethyl)quinazolin-4-ol (intermediate 1-8 NAN FaC OH CF, (1-8) A flask was charged with 2-amino-3,5-bis(trifluoromethyl)benzonitrile (I-7, 8.8 g, 35 mmol), formic acid (83 mL) and sulfuric acid (2.8 mL, 52 mmol, 1.5 equiv.) and the mixture was stirred at 50 °C for 3 hours. The reaction was then cooled to room temperature and poured slowly in 300 mL of ice-water and stirred for 15 minutes. Resulting solid was filtered off and dried, resulting in desired product (I-8) as an off-white solid (8.9 g, 91%). "H NMR (400 MHz, DMSO-d) 8 ppm: 'H NMR (400 MHz, Solvent) 5 ppm 8.31 - 8.47 (m, 2 H), 8.61 (s, 1H), 12.97 (brs, 1 H). LC-MS (method 3): retention time 0.90 min, m / z 283 [M+H*]. Step D: Preparation of 4-chloro-6,8-bis(trifluoromethylquinazoline (intermediate [-9} CF3 (1-9) To a solution of 6,8-bis(trifluoromethyl)quinazolin-4-ol (I-8, 0.5 g, 5.04 mmol) in thionyl chloride (8.87 mL) was added 5 drops of N,N-dimethylformamide. The reaction mixture was heated to 100 °C for 1 hour, at which point the reaction became homogeneous. The reaction was cooled and concentrated under reduced pressure to afford the desired product (1-9) which was used as such for the next step. H NMR (400 MHz, CDCls) 8 ppm: 8.50 (s, 1 H), 8.84 (s, 1 H), 9.33 (s, 1 H). 19F NMR (377 MHz, CDCls) 5 ppm: -62.86 (s, 1 F), -60.78 (s, 1 F). LC-MS (method 3): retention time 0.75 min, m / z 352 [M+H*]. Step E: Preparation of N-[1-(2-pyrimidin-2-y|-1,2.4-triazol-3-y) ethyl]-6.8-bis(trifluoromethyhquinazolin- 4-amine (compound P.18) = aH NON SN H oN F. 3 Reg N y \ NY CFs (P.16) A flask was charged with 4-chloro-6,8-bis(trifluoromethyl)quinazoline(l-9, 200 mg, 0.67 mmol), 1-(2- pyrimidin-2-yl-1,2, 4-triazol-3-yl)ethylammonium chloride (prepared as in W0O2019 / 197468) (201 mg, 0.80 mmol, 1.2 equiv), potassium carbonate (276 mg, 2.0 mmol, 3 equiv.) and acetonitrile (3 mL) and heated at 80 °C for 4 hours. The reaction was cooled, salts were removed by filtration and the resulting crude was concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) provided the desired product (P.16) as a beige solid (120 mg, 40%). "H NMR (400 MHz, CDCls) & ppm: 1.85 (d, J=6.97 Hz, 3 H), 6.71 (quin, J=6.97 Hz, 1 H), 7.49 (t, J=4.77 Hz, 1 H), 8.14 (5, 1 H), 8.16 (5, 1 H), 8.27 (br d, J=4.03 Hz, 1 H), 8.38 (s, 1 H), 8.68 (5, 1 H), 9.01 (d, J=4.77 Hz, 2 H). LC-MS (method 3): retention time 0.97 min, m / z 455 [M+H*]. Example 3: Preparation of 2-chloro-N-[14{2-pyrimidin-2-yl-1,2 4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quinazolin-4-amine (compound P.25) N 1 SN H SO NZ N NSN FC N NY JIS Cl Fz (P.25) Step A: Preparation of 6,8-bis(trifluoromethyl)quinazoline-2,4-diol (intermediate [1-10] CF, (1-10) A flask was charged with 2-amino-3,5-bis(trifluoromethyl)benzonitrile (I-7 prepared in Example 2, 2 g, 7.87 mmol) and dichloromethane (20 mL). To this mixture was added chlorosulfonyl isocyanate (0.85 mL, 9.44 mmol, 1.2 equiv.) and the resulting mixture was stirred for 3 hours. The reaction was concentrated under reduced pressure and the residue heated in water (50 mL) at 100 °C for 18 hours. The resulting white solid was isolated by filtration to provide the desired product (I-10) (800 mg, 34%). TH NMR (400 MHz, CDsCN) & ppm: 8.20 - 8.23 (m, 1 H), 8.50 (s, 1 H), 8.73 (brs, 1 H), 9.51 (brs, 1 H). Step B: Preparation of 2 4-dichloro-6,8-bis(trifluoromethyl)quinazoline (intermediate 1-11) CF3 I-11) A flask was charged with 6,8-bis(trifluoromethyl)quinazoline-2,4-diol (I-10, 100 mg, 0.34 mmol) and phosphorous oxychloride (0.32 mL, 3.4 mmol, 10 equiv.). To this mixture was then added N,N- diisopropylethylamine (0.118 mL, 0.67 mmol, 2 equiv.) and the resulting mixture was heated at 100 °C for 2 hours. The reaction was concentrated under reduced pressure and the crude material was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to provide the desired product (I-11) as an off-white solid (84 mg, 75%). TH NMR (400 MHz, CDaCN) 5 ppm: 8.66 (s, 1 H), 8.90 (s, 1 H). Step C: Preparation of 2-chloro-N-[1-(2-pyrimidin-2-yl-1,2 4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quinazolin-4-amine (compound P.25 N. 1 SN H gO NZ N N§-N F3C N, OE nc. CF3 (P.25) A flask was charged with 2,4-dichloro-8,8-bis(trifluoromethyl)quinazoline (I-11, 100 mg, 0.30 mmol), 1- (2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethylammonium chloride (prepared as in WO2019 / 197468) (68 mg, 0.27 mmol, 0.9 equiv), potassium carbonate (123 mg, 0.90 mmol, 3 equiv.) and acetonitrile (1.5 mL) and heated at 80 °C for 16 hours. The reaction was cooled, diluted with water and extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded the desired product (P.25) as a pale yellow solid (60 mg, 41% yield). "H NMR (400 MHz, DMSO-de) 8 ppm: 1.79 (d, J=6.72 Hz, 3 H) 6.38 (t, J=6.72 Hz, 1 H) 7.65 (t, J=4.65 Hz, 1H) 8.18 (s, 1 H) 8.37 (brs, 1 H) 8.99 (d, J=4.65 Hz, 2 H) 9.24 (br s, 1 H) 9.90 (br d, J=6.36 Hz, 1 H). LC-MS (method 4): retention time 1.09 min, m / z 489 [M+H"]. Example 4: Preparation of N-methyl-N-[1-(2-pyrimidin-2-yl-1,2 4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quinazolin-4-amine (compound P.27) = aN N ua SN mn PN > ro Jr 3 Or CFs CF3 (P.27) A flask was charged with N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quinazolin-4-amine (P.16 prepared in Example 2, 148 mg, 0.33 mmol), cesium carbonate (319 mg, 0.98 mmol, 3 equiv.), acetonitrile (1.3 mL) and iodomethane (0.041 mL, 0.65 mmol, 2 equiv.). The mixture was heated at 50 °C overnight. The reaction was cooled and diluted with water (10 mL). The mixture was extracted three times with ethyl acetate (3 x 10 mL) and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) provided the desired product (P.27) (92 mg, 60%). "H NMR (400 MHz, CDCls) & ppm: 1.98 (d, J=6.97 Hz, 3 H), 3.37 (s, 3 H), 6.89 (q, J=6.97 Hz, 1 H), 7.23 (t, J=4.95 Hz, 1 H), 8.11 (3, 1 H), 8.24 (d, J=6.60 Hz, 2 H), 8.57 (d, J=4.77 Hz, 2 H), 8.60 (5, 1 H). LC-MS (method 3): retention time 0.97 min, m / z 455 [M+H"*]. 19F NMR (376 MHz, CDCla) 5 ppm: -62.40 (s, 1 F), -61.33 (s, 1 F). LC-MS (method 3): retention time 1.01 min, m / z 469 [M+H*]. Example 5: 8-chloro-N-(cyclopropylmethyl)-2-methoxy-N-[1-(2-pyrimidin-2-yl-1,2 4-triazol-3- yl)ethyl]-6-(trifluoromethyl)quinazolin-4-amine (compound P.36) iv, JOPTOPYHTICINY = NCNOAY=IN-1 17] quinazolin-4-amine (compound P ki ~=N NN Ns YG Oo TV AN pl (P.36) Step A: Preparation of 8-chloro-4-[cyclopropylmethyl-[1-(2-pyrimidin-2-yl-1,2.4-triazol-3- ylethyllamino]-6-(triflucromethyl)-1H-quinazolin-2-one (intermediate 1-12] AVA hyl)-1H-quinazolin-2-one (intermedi 0 ~=N NN LORE. or 1 Y A FOF (1-12) A flask was charged with 2,8-dichloro-N-(cyclopropylmethyl)-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yhethyl]-6-(trifluoromethyl)quinazolin-4-amine (P.49 prepared analogously to P.25 in Example 3, 180 mg, 0.35 mmol) and acetic acid (1.8 mL). This mixture was stirred for 2 hours at 80 °C. The reaction was concentrated under reduced pressure and the residue purified by reverse-phase chromatography (acetonitrile in water) to provide the desired product (I-12) (90 mg, 52%). "H NMR (400 MHz, DMSO-de) 8 ppm: 0.02 - 0.07 (m, 1H), 0.09 - 0.16 (m, 1H), 0.25 - 0.32 (m, 1H), 0.35- 0.41 (m, 1H), 0.77 - 0.85 (m, 1H), 1.87 (d, 3H), 3.06 (dd, 1H), 3.36 (dd, 1H), 6.40 - 6.46 (m, 1H), 7.38 (t, 1H), 7.69 (s, 1H), 8.19 (5, 1H), 8.25 (s, 1H), 8.54 (d, 2H), 10.84 - 10.92 (m, 1H). Step B: Preparation of 8-chloro-N-(cyclopropylmethyl)-2-methoxy-N-[1-(2-pyrimidin-2-yl-1.2 4-triazol-3- ylethyll-6-(trifluoromethyl)guinazolin-4-amine (compound P.36) 7 LO IN-{CYOIOPIODYITTICTTI yi) -e-TTICINIOX) inazolin-4-amine (compound P.36) k ~=N NN N= PRD Regn Tv AN FelP (P.36) 8-Chloro-4-[cyclopropylmethyl-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethylJamino]-6-(trifluoromethyl)-1H- quinazolin-2-one (I-12, 35 mg, 0.07 mmol) was dissolved in acetonitrile (0.53 mL) and potassium carbonate (30 mg, 0.21 mmol, 3 equiv.), followed by dimethyl sulfate (7.5 uL, 0.08 mmol, 1.1 equiv) were added. The resulting mixture was heated at 80 °C for 5 hours. The reaction was cooled and filtered through celite with acetonitrile washes. The filtrate was concentrated under reduced pressure and the crude material was purified by reverse-phase chromatography (acetonitrile in water) to provide the desired product (P.36) (90 mg, 52%). H NMR (400 MHz, methanol-ds) 8 ppm: 0.23 (qd, 1H), 0.31 - 0.06 (m, 1 H), 0.55 - 0.39 (m, 2H), 0.94 -0.83 (m, 1H), 2.02 (d, 3H), 3.36 (dd, 1H), 3.56 (dd, 1H), 3.97 (s, 3H), 6.78 (q, 1H), 7.29 (t, 1H), 8.08 (d, 1H), 8.18 (s, 1H), 8.21 (d, 1H), 8.42 (d, 2H). LC-MS (method 4): retention time 1.17 min, m / z 505 [M+H*]. Example 6: Preparation of 6,8-dibromo-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyllquinazolin-4- amine (compound P.38) 2] Ns N H NZ 1 NN Br N SN Br (P.38) Step A: Preparation of N'-(2,4-dibromo-6-cyano-phenyl)-N.N-dimethyl-formamidine (intermediate 1-13) Br (1-13) To a solution of 2-amino-3,5-dibromobenzonitrile (CAS No. 68385-95-5, 150 mg, 0.54 mmol) in methanol (5 mL) was added 1,1-dimethoxy-N,N-dimethyl-methanamine (0.228 mL, 1.63 mmol, 3 equiv.) and the reaction was stirred at 80 °C for 1 hour. The mixture was concentrated under reduced pressure to obtain product (I-13) as a solid (179 mg, 99.5%) which was used directly in the next step. LC-MS (method 3): retention time 1.17 min, m / z 505 [M+H*]. Step B: Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanone (intermediate I-14’ I) Ny N ry (1-14) A flask was charged with tributyl(pyrimidin-2-yl)stannane (CAS No. 153435-63-3, 25 g, 67.7 mmol, 1 equiv.), 1-(3-chloropyrazin-2-yl)ethanone (CAS No. 2142-68-9, 12.37 g, 71.12 mmol, 1.05 equiv.) and toluene (500 mL). Reaction mixture was purged with nitrogen for 10 minutes and then copper(l) iodide (2.58 g, 13.55 mmol, 0.2 equiv.) and tetrakis(triphenylphosphine)palladium(0) (3.81 g, 3.38 mmol, 0.05 equiv.) were added. The reaction was then heated at 95 °C for 5 hours. The mixture was cooled, filtered through a pad of celite with ethyl acetate washings and the filtrate was concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded product (I-14) as a brown solid (10 g, 51.6%). LC-MS (method 4): retention time 0.37 min, m / z 201 [M+H*]. Step C: Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine (intermediate I-15) Fa Ng N YX HANNAN NS (1-15) A flask was charged with 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanone (I-14, 500 mg, 2.5 mmol, 1 equiv.), ammonium acetate (3.85 g, 50.0 mmol, 20 equiv.) and ethanol (25 mL). Next aq. NH (28%) (7.5 mL) and sodium cyanoborohydride (0.50 g, 7.5 mmol, 3 equiv.) were added and the mixture was heated at 80 °C for 2 hours. The mixture was cooled and concentrated under reduced pressure. Purification of the crude material by reverse-phase column chromatography (C18 40-60 pm, acetonitrile in water) afforded product (I-15) as a brown gum (210 ma, 42%). "H NMR (400 MHz, DMSO-de) 8 ppm: 1.50 (d, J=6.6 Hz, 3H), 4.93 (d, J=6.6 Hz, 1H), 7.70 (t, J=5.0 Hz, 1H), 8.86 (d, J=2.3 Hz, 1H), 8.90 (d, J=2.4 Hz, 1H), 9.07 (d, J=4.9 Hz, 2H). Step D: Preparation of 6,8-dibromo-N-[1-(3-pyrimidin-2-ylpyrazin-2-ylethyllquinazolin-4-amine ‘compound P.38] AN Ny N H NN | NN Br N SN Br (P.38) A vial was charged with 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanone (I-15, 120 mg, 0.59 mmol, 1.1 equiv.), N'-(2,4-dibromo-6-cyano-phenyl)-N,N-dimethyl-formamidine (1-13, 179 mg, 0.54 mmol, 1 equiv.) and acetic acid (2.7 mL). The mixture was stirred at 120 °C for 1 hour. Another batch of 1-(3- pyrimidin-2-ylpyrazin-2-yl)ethanone (I-15, 135 mg) was added and the stirring continued till reaction completion. The mixture was cooled, diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate aqueous solution, dried over sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane), followed by reverse-phase purification (acetonitrile in water) afforded the desired product (I-7) as a brown solid (83 mg, 32%). "H NMR (400 MHz, DMSO-d) 5 ppm: 1.71 (d, J=6.97 Hz, 3 H), 5.92 (quin, J=6.79 Hz, 1 H), 7.53 (t, J=4.77 Hz, 1 H), 8.15 (5, 1 H), 8.28 (d, J=1.83 Hz, 1 H), 8.65 (d, J=1.83 Hz, 1 H), 8.66 (d, J=2.57 Hz, 1 H), 8.74 (d, J=2.20 Hz, 1 H), 8.77 (d, J=6.97 Hz, 1 H), 8.92 (d, J=5.14 Hz, 2 H). LC-MS (method 3): retention time 0.87 min, m / z 488 [M+H"]. Example 7: Preparation of 6-[5-[1-[[2-methyI-6.8-bis(trifluoromethyl)quinazolin-4- yllamino]ethyl]-1,2.4-triazol-1-yl]pyridine-3-carbonitrile (compound P.60) i — NN XX OY ; H No CFs CF; (P.60) Step A: Preparation of 2-methy|-6,8-bis(trifluoromethyl)quinazolin-4-amine (intermediate |-16’ NN rT CF, (1-16) A sealed tube was charged with 2-amino-3,5-bis(trifluoromethyl)benzonitrile (I-7 prepared in Example 2,300 mg, 1.18 mmol) and acetamide (0.7 g, 11.8 mmol, 10 equiv.). The mixture was stirred at 180 °C for 4 days. The reaction was then cooled to room temperature and diluted with water (25 mL). The mixture was extracted three times with ethyl acetate (3 x 20 mL) and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude material was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to provide desired product (I-16) as a pale yellow solid (102 mg, 29%). 19F NMR (377 MHz, DMSO-ds) 5 ppm: -60.36 (s, 1 F), -59.63 (s, 1 F). LC-MS (method 3): retention time 0.95 min, m / z 296 [M+H*]. Step B: Preparation of 6-[5-(1-bromoethyl)-1.2 4-triazol-1-yl|pyridine-3-carbonitrile (intermediate I-18) ar NSN Br NY, mn aN 0 - (I-17) oo (1-18) To a solution of 2-Bromopropanamide (CAS No. 5875-25-2, 4.00 g, 26.3 mmol, 1 equiv.) in dichloromethane was added N,N-Dimethylformamide dimethyl acetal (CAS No. 4637-24-5, 5.58 mL. 39.5 mmol, 1.5 equiv.). The mixture was heated to reflux for 30 minutes. The reaction was then cooled to room temperature and concentrated under reduced pressure to provide crude desired product 2- bromo-N-(dimethylaminomethylene)propanamide (I-17) as a yellow oil (5.6 g, 98%) which was used as such in the next step. H NMR (400 MHz, CDCls) 6 ppm: 1.85 (d, J=6.97 Hz, 3 H), 3.14 (d, J=0.73 Hz, 3H), 3.17 (5, 3 H), 4.55 (q, J=6.85 Hz, 1 H), 8.49 (5, 1 H). To a solution of 2-bromo-N-(dimethylaminomethylene)propenamide (I-17, 5.40 g, 24 mmol, 1 equiv.) in 1,4-dioxane (54 mL) was added 5-cyano-2-hydrazinopyridine (CAS No. 104408-24-4, 4.68 g, 25.2 mmol, 1.05 equiv.). Next, acetic acid (54 mL) was added slowly. The resulting red solution was heated to 80 °C for 1 hour. The reaction was cooled and concentrated under reduced pressure. The mixture was then taken up in ethyl acetate and washed with a saturated aqueous sodium bicarbonate solution and water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded the desired product (I-18) as a white solid (3.1 g, 46%). "H NMR (400 MHz, CDCl) 3 ppm: 2.26 (d, J=6.97 Hz, 3 H), 6.43 (q, J=6.97 Hz, 1 H), 8.05 (s, 1 H), 8.14 - 8.20 (m, 2 H), 8.85 (dd, J=1.83, 1.10 Hz, 1 H). LC-MS (method 3): retention time 0.88 min, m / z 278-280 (Br pattern) [M+H*]. Step C: Preparation of 6-[5-[1-[[2-methyI-6,8-bis(trifluoromethyhquinazolin-4-yllamino]ethyl]-1,2,4- triazol-1-yllpyridine-3-carbonitrile (compound P.60) ~ NAN C OT H Nv CF, CFs (P.60) A sealed tube was charged with 2-methyl-6,8-bis(trifluoromethyl)quinazolin-4-amine (I-16, 106 mg, 0.36 mmol), acetonitrile (1.43 mL), cesium carbonate (351 mg, 1.08 mmol, 3 equiv.) and 6-[5-(1- bromoethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (I-18, 110 mg, 0.40 mmol, 1.1 equiv.) and the reaction mixture was heated to 50 °C for 3 h. The reaction was cooled, diluted with water (60 mL) and extracted three times with ethyl acetate (3 x 60 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded the desired product as a yellow solid (134 mg, 76% yield). "H NMR (400 MHz, DMSO-de) 6 ppm: 1.49 - 1.58 (m, 3 H), 4.09 - 4.19 (m, 1 H), 6.49 - 6.55 (m, 1 H), 7.13-7.22 (m, 1H), 7.63 - 7.71 (, 1 H), 7.83 - 7.90 (m, 1 H), 8.17 - 8.24 (m, 1 H), 8.60 - 8.66 (m, 1 H), 9.23 - 9.29 (m, 1 H). LC-MS (method 3): retention time 1.16 min, m / z 494 [M+H*]. Example 8: Preparation of 6,8-dichloro-N-[1-(2-pyrimidin-2-yl-1,2 4-triazol-3-yl)ethyllquinolin-4- amine (compound P.67) = aN N H N / A N NAY Y cl N NN Cl Cl (P.67) To a solution of 6,8-dichloroquinolin-4-amine (100 mg, 0.469 mmol) in N,N-dimethylformamide (0.94 mL) was added portionwise at room temperature sodium hydride (20.7 mg, 0.516 mmol, 1.10 equiv.). The reaction mixture was kept stirring at this temperature for 10 minutes. A solution of 2-[5-(1- bromoethyl)-1,2,4-triazol-1-yl]pyrimidine (intermediate I-20 prepared as described before, 125 mg, 0.493 mmol, 1.05 equiv.) in N,N-dimethylformamide (0.94 mL) was then added dropwise to the reaction mixture and it was stirred at room temperature for 1 hour. It was poured into water and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (ethyl acetate in cyclohexane, then methanol in dichloromethane) afforded the desired product as a pale orange solid (39 mg, 0.10 mmol). H NMR (400 MHz, chloroform-d) & ppm: 1.75 — 1.84 (m, 3 H) 6.08 — 6.20 (m, 1 H) 6.28 — 6.37 (m, 1 H) 6.51 — 6.58 (m, 1 H) 7.45 = 7.51 (m, 1 H) 7.75 — 7.86 (m, 2 H) 8.17 — 8.12 (m, 1 H) 8.60 — 8.66 (m, 1H) 8.94 — 9.02 (m, 2H). LC-MS (method 1): retention time 0.63 min, m / z 386-390 [M+H"] (dichloro pattern). Example 9: Preparation of 6.8-dichloro-N-[1-(2-pyrimidin-2-yl-1,2.4-triazol-3-yl)ethyllquinazolin- 4-amine (compound P.68) =N NN bo NSN YX] hy "OW i | (P.68) Step A: Preparation of 2-[5-(1-bromoethyl)-1.2 4-triazol-1-yllpyrimidine (intermediate 1-20) =N nN N Ny Br BN NW 0 (1-19) (1-20) To a solution of 2-bromopropanamide (CAS 5875-25-2, 1.50 g, 9.38 mmol) in dichloromethane (37.5 mL) was added at room temperature 1,1-dimethoxy-N,N-dimethyl-methananime (CAS 4637-24-5, 2.49 mL, 18.8 mmol, 2.00 equiv.). The reaction mixture was heated up to 40 °C and stirred for 2.5 hours. After cooling down to room temperature, the reaction mixture was concentrated under reduced pressure to afford quantitatively crude intermediate (I-19). LC-MS (method 1): retention time 0.26 min, m / z 207-209 [M+H*] (Br pattern). A mixture of intermediate 1-1 (1.94 g, 9.38 mmol), acetic acid (28.1 mL) and pyrimidin-2-ylhydrazine (1.24 g, 11.3 mmol, 1.20 equiv.) was heated up to 65 °C and stirred for 2 hours. After cooling down to room temperature, the reaction mixture was concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded the desired product (I-20) as a pale yellow solid (1.70 g, 6.69 mmol). "H NMR (400 MHz, chloroform-d) 3 ppm: 2.20 — 2.31 (m, 3 H) 6.34 — 6.48 (m, 1 H) 7.37 = 7.45 (m, 1 H) 8.05 — 8.15 (m, 1 H) 8.88 — 8.95 (m, 2 H). LC-MS (method 1): retention time 0.66 min, m / z 254-256 [M+H*] (Br pattern). Step B: Preparation of 6 8-dichloro-N-[1-(2-pyrimidin-2-yl-1,2 4-triazol-3-ylethyllquinazolin-4-amine (compound P.68) = AN (0 NN NeN | N “OY N H No Ci (P68) To a solution of 6,8-dichloroquinazolin-4-amine (400 mg, 1.87 mmol) in acetonitrile (7.47 mL) were added at room temperature cesium carbonate (1.83 g, 5.61 mmol, 3.00 equiv.) and 2-[5-(1- bromoethyl)-1,2,4-triazol-1-yl]pyrimidine (intermediate 1-20 prepared as described before, 522 mg, 2.06 mmol, 1.10 equiv.). The reaction mixture was heated up to 50 °C and stirred ovemight. After cooling down to room temperature, the reaction mixture was diluted with water and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude material by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded the desired product as a yellow solid (351 mg, 0.907 mmol). LC-MS (method 1): retention time 0.81 min, m / z 387-391 [M+H"] (dichloro pattern). Example 10: Preparation of N-[1{2-pyrimidin-2-yl-1,2 4-triazol-3-yl)ethyl]-5,7- bis(trifluoromethyl)isoquinolin-1-amine (compound P.83) = aH N 1 SN iz we C0 3 NN CF3 CF3 (P.83) Step A: Preparation of 2-iodo-3,5-bis(trifluoromethyl)benzonitrile (intermediate 1-21) FsC : AN CFs (1-21) 2-Amino-3,5-bis(trifluoromethyl)benzonitrile (1-7, prepared as in Example 2, 2.19 g, 8.62 mmol, 1 equiv.) was dissolved in diiodomethane (6.9 mL) and acetonitrile (13.8 mL). Isoamylnitrite (2.3 mL, 16.4 mmol, 1.9 equiv.) was then added under an argon atmosphere. The reaction was stirred at 50 °C for 60 minutes, then at 80 °C for another 60 minutes. The reaction was concentrated under reduced pressure and diluted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a crude mixture of oil and solid. The oil was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) and the resulting solid combined with the crude solid material to afford desired product (I-21) (2.2 g, 70%). H NMR (400 MHz, CDCls) 5 ppm: 7.99 - 8.02 (m, 1 H), 8.03 - 8.07 (m, 1 H). Step B: Preparation of 3,5-bis(trifluoromethyl)-2-(2-trimethylsilylethynvl)benzaldehvde (intermediate |- 23) si” I o lo “CY gr CFa CFa (1-22) (1-23) 2-iodo-3,5-bis(trifluoromethyl)benzonitrile (I-21 prepared above, 3.52 g, 9.64 mmol, 1 equiv.) was dissolved in toluene (72 mL) and the solution cooled to -78 °C and stirred for 90 minutes. The reaction was warmed to room temperature and quenched by the slow addition of aqueous hydrochloric solution (1M, 50 mL). The mixture was extracted with ethyl acetate (50 mL) and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford crude 2-iodo-3,5-bis(trifluoromethyl)benzaldehyde (I-22) which was used as such for the next step. 2-iodo-3,5-bis(trifluoromethyl)benzaldehyde (I-22 prepared above, 3.5 g, 9.51 mmol, 1 equiv.) was dissolved in triethylamine (47.5 mL) under an Ar atmosphere. Next, copper (l) iodide (0.073 g, 0.38 mmol, 0.04 equiv.), bis(triphenylphosphine)palladium(ll) dichloride (0.135 g, 0.19 mmol, 0.02 equiv.) and trimethylsilylacetylene (3.39 mL, 23.8 mmol, 2.5 mmol) were added successively and the mixture was stirred at 80 °C. After 17 hours, the reaction was cooled, concentrated under reduced pressure and the material was dissolved in ethyl acetate. The organic layer was washed twice with dilute aqueous hydrochloric solution (2 x 20 mL), brine and then filtered and concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded desired product (I-23) (1.076 g, 33%). "H NMR (400 MHz, CDCls) & ppm: 6.33 (brs, 1 H), 7.97 (brs, 1 H), 8.33 (s, 1 H), 8.66 (brs, 1 H), 11.57 (brs, 1 H). LC-MS (method 3): retention time 1.34 min, m / z 339 [M+H*]. Step C: Preparation of 5,7-bis(trifluoromethyl)isoquinoline (intermediate 1-24’ CF (1-24) 3,5-bis(trifluoromethyl)-2-(2-trimethylsilylethynyl)benzaldehyde (I-23 prepared above, 1.075 g, 3.18 mmol, 1 equiv.) was weighed in a microwave tube and ammonia solution (7M in methanol, 10 mL) was added. The tube was capped and irradiatd in a microwave reactor for 15 minutes at 130 °C. The solvent was then removed under reduced pressure to afford desired product (I-24) (820 mg, 97%). TH NMR (400 MHz, CDCl) 5 ppm: 7.99 - 8.10 (m, 1 H), 8.26 (s, 1 H), 8.53 (s, 1 H), 8.85 (d, J=6.24 Hz, 1H), 9.50 (s, 1 H). LC-MS (method 3): retention time 1.05 min, m / z 266 [M+H"]. Step D: Preparation of 2-oxido-5.7-bis(trifluoromethylisoquinolin-2-ium (intermediate 1-25) CFs (1-25) 5,7-bis(trifluoromethyl)isoquinoline (I-24 prepared above, 875 mg, 3.3 mmol, 1 equiv.) was taken in acetic acid (5.5 mL) and H202 (35 wt%) (0.85 mL, 9.9 mmol, 3 equiv.) was added. The mixture was then heated to 70 °C. After 17 hours, the reaction was cooled and diluted with ethyl acetate and water and NaOH (4M) was added until pH 12 was reached. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford desired product (1-25) (1.040 g, quantitative). H NMR (400 MHz, CDCls) § ppm: 'H NMR (400 MHz, Solvent) & ppm 8.05 (br d, J=7.34 Hz, 1 H), 8.08 (s, 1 H), 8.20 (s, 1 H), 8.36 (dd, J=7.52, 1.65 Hz, 1 H), 8.90 (s, 1 H). LC-MS (method 3): retention time 0.85 min, m / z 282 [M+H*]. Step E: Preparation of N-[1-(2-pyrimidin-2-yl-1,2.4-triazol-3-yl) ethyl]-5,7-bis(trifluoromethylisoquinolin- 1-amine (compound P.83’ {J N 7 N yh FsC N n ’ Sd Cc. CF5 (P.83) To a flask containing 2-oxido-5,7-bis(trifluoromethyl)isoquinolin-2-ium (I-25 prepared above, 50 mg, 0.18 mmol. 1 equiv.) and 1-(2-pyrimidin-2-yl-1,2 4-triazol-3-yl)ethanamine hydrochloride (prepared analog to W02019 / 197468 page 128, 80.6 mg, 0.356 mmol, 2 equiv.) dissolved in dichloromethane (0.89 mL) was added N,N-diisopropylethylamine (0.155 mL, 0.88 mmol, 5 equiv.) and bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP®, 211 mg, 0.44 mmol, 2.5 equiv.) and the reaction stirred at room temperature. After 4 hours, more N,N-diisopropylethylamine (0.155 mL, 0.89 mmol, 5 equiv.) and bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP®, 211 mg, 0.44 mmol, 2.5 equiv.) were added. After 17 hours, the reaction was filtered and the crude purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to provide desired product P.38 (30 mg, 37%). "H NMR (400 MHz, CDCls) & ppm: 1.84 (d, J=6.60 Hz, 3 H), 6.15 - 6.97 (m, 1 H), 6.56 (quin, J=7.06 Hz, 1H), 7.04 (dd, J=5.69, 2.02 Hz, 1 H), 7.44 (t, J=4.77 Hz, 1 H), 7.63 (br d, J=7.34 Hz, 1 H), 7.92 (d, J=6.24 Hz, 1 H), 7.94 (brs, 1 H), 8.10 (5, 1 H), 8.41 (5, 1 H), 8.98 (d, J=4.77 Hz, 2 H). 9F NMR (377 MHz, CDCl3) § ppm: -62.15 (s, 1 F), -61.08 (s, 1 F). LC-MS (method 3): retention time 1.08 min, m / z 454 [M+H*]. Example 11: Preparation of 6-[5-[(1R)-1-[[6.8-bis(triflucromethylicinnolin-4-yllaminolethyl]- 1,2. 4-triazol-1-yl]pyridine-3-carbonitrile (compound P. 135) Step A: Preparation of 6 8-bis(trifluoromethyl)cinnoline-4-ol (1-26) ph F 1-[2-amino-3,5-bis(trifluoromethyl)phenyllethanone (CAS-No.: 1805121-99-6, 1.25g, 4.61mmol, 1eq) was dissolved in glacial acetic acid (18.4ml) and Sulfuric acid 70% (0.92ml, 12.1mmol, 2.63eq). The solution was cooled to 22°C and a ice cold solution of sodium nitrite (389mg, 5.53mmol, 1.2eq) in water (3.55mi) was added dropwise under cooling. After 45min Triethylamine (1.81mi, 12.91mmol, 2.8eq) was added and the reaction was stirred at room temperature for 17h. It was poured on 100ml ice water and it was extracted with Ethylacetate (2x60ml). The combined organic layer was washed saturated Na2COa-solution and brine, it was dried over anhydrous MgSOs and concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded desired product (I-26) (907mg, 63%). H NMR (400 MHz, CDCls) 6 ppm: 10.32 (br s, 1H) 8.79 (s, 1H) 8.21 (5, 1H) 7.99 (s, 1H). 19F NMR (377 MHz, CDCl) 8 ppm: -80.61 (s, 3F) -62.65 (s, 3F). LC-MS (method 3) retention time 0.88min m / z 283 [M+H*]. Step B: Preparation of 4-chloro-6.8-bis(trifluoromethyl)cinnoline (1-27) ANE F 6,8-bis(trifluoromethyl)cinnolin-4-ol (I-26, 840mg, 2.98mmol, 1eq) was suspended in Toluene (5.95ml) and Phosphoryl trichloride (0.31mi, 3.28mmol, 1.1eq) was added. The mixture was heated to 50°C for 17h. The reaction was quenched with sat. Ammonium chloride solution and diluted with Ethylacetate. The pH was adjusted with aqueous Ammonia to 10-12. The organic layer was washed five times with brine. It was dried over anhydrous MgSO and concentrated under reduced pressure to give (I-27) (1.04g, 93% yield, 80% purity). TH NMR (400 MHz, CDCls) 5 ppm: 9.67 (s, 1H) 8.78 (s, 1H) 8.43 (s, 1H). 19F NMR (377 MHz, CDCla) 5 ppm: -59.6 (s, 3F) -63.4 (s, 3F). LC-MS (method 3) retention time 1.11min m / z 301 [M+H*]. Step C: Preparation of (25)-2-[[6.8-bis(trifluoromethyl)cinnoline-4-yllamino]propenamide (I-28 oO -[[6,8-bis (trifluoromethyl cinnoline-4-yllamir N. Fo NZ F I | NH; F =z N | H xn o 2 ANG F 4-chloro-6,8-bis(trifluoromethyl)cinnoline (I-27, 1.04g, 3.46mmol, 1eq), Potassium carbonate (2.39g, 17.3mmol, 5eq) and (2S)-2-aminopropanamide;hydrochloride (2.22g, 17.3mmol, 5eq) were heated to 50°C in NMP (13.8ml) for 60h. The reaction mixture was diluted with water (100ml) and Ethyl acetate (100ml). The organic layer was washed with water (30mi), brine (30mi), dried with anhydrous NazSO4 and concentrated under reduced pressure to yield (I-28) (1.57g, 73%) H NMR (400 MHz, DMSO-a8) & ppm: 9.35 (s, 1H) 8.78 (s, 1H) 8.38-8.19 (m, 2H) 7.76 (s, 1H) 7.29 (5, 1H) 4.41 (quin, J = 7.0Hz, 1H) 1.56 (d, J = 7.0Hz, 3H) 18F NMR (377 MHz, DMSO-d6) & ppm: -58.9 (s, 3F) -60.9 (s, 3F) LC-MS (method 3): retention time 0.86 min, m / z 353 [M+H*]. Step D: Preparation of (NE 2S)-2-[[6.8-bis(trifluoromethyl)cinnolin-4-yllamino]-N- (dimethylaminomethylene)propenamide (I-29) | N, ro Oo et NER ir TY NY xn 0 ANE F (28)-2-[[6,8-bis(trifluoromethyl)cinnolin-4-ylJamino]propenamide (I-28, 500mg, 1,42mmol, 1eq) was mixed with 2-Methyltetrahydrofuran (14.2ml) and DMF-DMA (377pl, 2.84mmol, 2eq) and heated to 50°C for 30min. The reaction mixture was evaporated under reduced pressure to yield (I-29) (642mg, 99%). LC-MS (method 3): retention time 0.92 min, m / z 408 [M+H"]. Step E: Preparation of 6-[5-[(1R)-1-][6.8-bis(trifluoromethylcinnolin-4-yllaminolethyll-1.2 4-triazol-1- yllpyridine-3-carbonitrile (compound P. 135) PY ANE Fo J rANe ~ = 7 (NE, 28)-2-[[6,8-bis(trifluoromethyl)cinnolin-4-ylJamino]-N-(dimethylaminomethylene)propenamide (I 29, 306mg, 0.75mmol, 1eq) was dissolved in 2-Methyltetrahydrofuran (3ml). 6-Hydrazinylnicotinonitrile (191mg, 1.35mmol, 1.8eq) and acetic acid (1.88mi) were added. The mixture was heated to 70°C for 1h. It was cooled to 25°C and it was diluted with Ethylacetat (30m). It washed with water, saturated NazCOz-solution and brine, it was dried over anhydrous Na2SOs and concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane), followed by reverse-phase purification (acetonitrile in water) afforded the desired product (P. 135) (87mg, 24%). H NMR (400 MHz, CDCls) § ppm: 9.03-8.99 (m, 2H) 8.94 (br s, 1H) 8.30 (s, 1H), 8.27-8.23 (m, 2H) 8.06 (5, 1H) 6.44 (q, J = 6.6Hz, 1H) 1.95 (d, J = 6.6Hz, 3H). °F NMR (377 MHz, CDCls) § ppm: -60.14 (s, 3F) -62.78 (s, 3F). LC-MS (method 3): retention time 1.01 min, m / z 480 [M+H"]. Example 12: Preparation of 4-[[(18)-1-[2-(5-cyano-2-pyridyl)-1,2 4-triazol-3-yl]ethyl]amino]-6,8- bis(trifluoromethyl)quinoline-3-carbonitrile (compound P.139) A H ~ 7 ¢ 7 Tg Peo My Dr Ar F Step A: Preparation of Ethyl (2)-3-[2 4-bis(trifluoromethylanilino]-2-cyano-prop-2-enoate (compound I- 30) F =\ H -—f 0 od / F JN F— F F A mixture of Ethyl (ethoxymethylene)cyanoacetate (1.46g, 8.47mmol, 2eq) and 2,4- Bis(trifluoromethyl)aniline (1g, 4.23mmol, 1eq) was heated to 140°C for 1h. The mixture was cooled to 25°C and it was washed with a mixture of TBME: Cyclohexane 30:70. The solid was filtered off and dried to give (I-30) (490mg, 33%). H NMR (400 MHz, DMSO-a8) 5 ppm: 11.34 (br d, J = 12.5Hz, 1H) 8.82 (d, J = 12.4Hz, 1H) 810-8.18 (m, 2H) 8.05 (s, 1H) 4.28 (q, J = 7.2Hz, 2H) 1.28 (t, J = 7.1Hz, 3H). LC-MS (method 4): retention time 1.19 min, m / z 353 [M+H*]. Step B: Preparation of 4-0x0-68-bis(trifluoromethyl)-1H-quinoline-3-carbonitrile (compound 1-31 ZN wr ~ Jd he fr NY F = o S$ 1 ANE F Ethyl (2)-3-[2,4-bis(trifluoromethyl)anilino]-2-cyano-prop-2-enoate (I-30, 500mg, 1.42mmol, 1eq) was heated in Phenyl ether-biphenyl eutectic (2.5ml) to 260°C for 8h. After cooling to room temperature it was diluted with Cyclohexane to precipitate the product. It was washed with tert-butyl methyl ether and dried under reduced pressure to give (I-31) (180mg, 41%). H NMR (400 MHz, DMSO-d6) 5 ppm: 8.68 (s, 1H) 8.66 (s, 1H) 8.45 (s, 1H). LC-MS (method 4): retention time 0.95 min, m / z 307 [M+H"]. Step C: Preparation of 4-chloro-6.8-bis(trifluoromethyl)quinoline-3-carbonitrile (compound 1-32) ZN Zz zz ce FON E “7 Cl XX F— —F F 4-0x0-8,8-bis(trifluoromethyl)-1H-quinoline-3-carbonitrile (I-31, 600mg, 1.96mmol, 1eq) and Thionyl chloride (6ml, 80.6mmol, 41eq) were mixed together with N,N-dimethylformamide (30ul, 0.38mmol, 0.2eq). The mixture was heated to 80°C for 3h. It was concentrated under reduced pressure and it was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to give (I-32) (423mg, 66%). TH NMR (400 MHz, CDCls) 5 ppm: 9.24 (s, 1H) 8.86 (s, 1H) 8.47 (s, 1H). LC-MS (method 4): retention time 1.16 min, m / z 325 [M+H*]. Step D: Preparation of tert-butyl N-[(18)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo- ethyllcarbamate (compound [1-33] oO 0 SLA ASA H 0 tert-butyl N-[(1S)-2-amino-1-methyl-2-oxo-ethyljcarbamate (70g, 353mmol, 1eq) was mixed with 2- Methyltetrahydrofuran (1.12l) and DMF-DMA (70ml, 530mmol, 1.5eq) and heated to 40°C for 2h. The reaction mixture was concentrated under reduced pressure to yield (1-33) (105g, 97% yield, 80% purity). 'H NMR (400 MHz, CDCl) 5 ppm: 8.38 (s, 1H) 5.98-6.15 (m, 1H) 4.25-4.37 (m, 1H) 3.16 (s, 3H) 3.09 (s, 3H) 1.46 (s, 9H) 1.40 (m, 3H). Step E: Preparation of N-[(15)-1-[2-(5-cyano-2-pyridyl)-1,2 4-triazol-3-yllethyllcarbamate (compound I- 34) ? N A aw A~ Tert-butyl N-[(18)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethylJcarbamate (I-33, 80% purity, 50g, 164mmol, 1eq) was dissolved in 1,4-Dioxane (510ml). To this was added 6- hydrazinopyridine-3-carbonitrile (33.1g, 247mmol, 1.5eq) and glacial acetic acid (510ml). The mixture was heated to 90°C for 30min. After cooling to 25°C the reaction mixture was concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) gave (I-34) (23g, 32%) H NMR (400 MHz, CDCls) 5 ppm: 8.80 (dd, J = 1.90, 0.8Hz, 1H) 8.10-8.20 (m, 1H) 7.98 (s, 1H) 5.92 6.02 (m, 1H) 5.77 (brd, J = 8.6Hz, 1H) 4.12 (q, J = 7.1Hz, 2H) 1.58 (d, J = 6.8Hz, 3H) 1.42 (s, 6H). Step F: Preparation of [(18)-1-[2-(5-cyano-2-pyridyl)-1.2.4-triazol-3-yllethyllammonium:2.2.2- trifluoroacetate (compound [-35) = H ’ SAN HY | | N H Nd A yr E H Tert-butyl N-[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyljcarbamate (I-34, 1.1g, 3.5mmol, 1eq) was dissolved in Methanol (11ml) and Trifluoroacetic acid (5.86mi, 70mmol, 20eq) was added. The mixture was stirred at 25°C for 2h. The reaction mixture was concentrated under reduced pressure. MTBE was added to the crude oil and it was stirred for 5min. The MTBE was decanted and second time MTBE was added. The product precipitated out, it was filtered off and dried to yield (I-35) (600mg, 50%). LC-MS (method 5): retention time 0.31 min, m / z 215 [M+H*]. Step G: Preparation of 4-[[(18)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yllethyllamino]-6,8- bis(trifluoromethyl)quinoline-3-carbonitrile (compound P.139) A CN H Coll oN | NN NT \ N R \ N F \ Dr PAF F In a round bottom flask [(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yllethyllammonium;2,2,2- trifluoroacetate (I-34, 546mg, 1.66mmol, 1.2eq), 4-chloro-8,8-bis(trifluoromethyl)quinoline-3- carbonitrile (I-32, 450 mg, 1.3863 mmol, 1eq) and Potassium carbonate (581mg, 4.16mmol, 3eq) were suspended in Acetonitrile (9ml). The reaction mass were heated to 60°C for 2h. The reaction mass was quenched with water and stirred for 20min. P. 139 (432mg, 62%) precipitated as a solid which was filtered, washed with water and was dried under reduced pressure. H NMR (400 MHz, DMSO-a8) 5 ppm 9.30 (s, 1 H) 8.95 (d, J=7.8Hz, 1H) 8.89-8.93(m, 1 H) 8.73 (s, 1 H) 8.49 (dd, J=8.6, 2.1Hz, 1 H) 8.35(s, 1 H) 8.31 (s, 1 H) 8.07 (d, J = 8.7Hz, 1 H) 6.58 (t, J = 7.1Hz, 1 H) 1.91 (d, J = 6.6Hz, 3 H). 19F NMR (377 MHz, DMSO-d6) 5 ppm -59.16 (s, 3F) , -60.26 (s, 3F). LCMS (method 4): retention time: 1.18 min, m / z 503 [M+H*]. Example 13: Preparation of 6-chloro-N-methyl-8-(trifluoromethyl)-N-[(18)-1-[2-[5-[4- {trifluoromethyljthiazol-2-yl]-2-pyridyl]-1,2,4-triazol-3-ylJethyl]quinazolin-4-amine (compound P. 142) RF YY =~ A $ / rs VV N, = N \ OT Cl Step A: Preparation of 6-[5-[(18)-1-[[6-chloro-8-(trifluoromethyhquinazolin-4-yllaminolethyl]-1.2,4- triazol-1-yllpyridine-3-carbonitrile (1-36 = w F I" Il HH | ef) Y 2 N E N \ 2eRRT Cl A flask was charged with 4 6-dichloro-8-(trifluoromethyl)quinazoline (CAS-No.: 1565368-05-9, 100mg, 0.37mmol, 1eq), [(1S)-1-[2-(5-cyano-2-pyridyl)-1,2 4-triazol-3-yllethyllammonium;2,2 2-trifluoroacetate (1-35 from example 12, 74% purity, 199mg, 0.45mmol, 1.2eq), cesium carbonate (366mg, 1.12mmol, 3eq) and acetonitrile (1ml). The reaction mass was stirred at 25°C for 16h. It was diluted with water and extracted with two times with ethyl acetate. The combined organic layer was washed with brine, dried aver anhydrous Na2SOs and concentrated under reduced pressure. The crude material was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to provide desired product (I-36). (107mg, 64%). "H NMR (400 MHz, DMSO-d6) & ppm: 9.11 (d, J = 6.9Hz, 1H) 9.04 (d, J = 1.5Hz, 1H) 8.98-9.00 (m, 1H) 8.93 (d, J = 2.2Hz, 1H) 8.57 (dd, J = 8.6, 2.2Hz, 1H) 8.34 (s, 1H) 8.18-8.23 (m, 2H) 8.06-8.10 (m, 1H) 6.37 (t, J = 6.85Hz, 1H) 1.74 (, J = 7.0Hz, 3H). LCMS (method 4): retention time: 1.07 min, m / z 445 [M+H"]. Step B: Preparation of 6-[5-[(18)-1-[[6-chloro-8-(trifluoromethyhquinazolin-4-yl]-methyl-aminolethyll- 1,2 4-triazol-1-yl]pyridine-3-carbonitrile (1-37) = Ww Ix | FS YN NM F A N Ny OO N Ci 6-[5-[(18)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]Jamino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile (I-36, 1.40g, 3.15mmol, 1eq) was weighed in a sealeable tube together with Acetonitrile (15.7ml), cesium carbonate (3.08g, 9.44mmol, 3eq) and iodomethane (396, 6.29mmol, 2eq). The tube was closed and heated to 50°C for 16h. After cooling to 25°C it was extracted two times with ethyl acetate. It was washed with water and brine, dried over anhydrous MgSOs and concentrated under reduced pressure. It was purified by flash chromatography over silica gel (ethyl acetate in dichloromethane 3:1) to give (I-37). "H NMR (600 MHz, DMSO-d6) & ppm 8.50 (dd, J = 8.5, 2.20Hz, 1H) 8.45 (s, 2H) 8.32 (s, 1H) 8.32 (s, 1H) 8.22 (d, J = 1.9Hz, 1H) 8.09 (d, J = 2.1Hz, 1H) 8.05 (d, J = 8.5Hz, 1H) 6.67 (q, J = 6.9Hz, 1H) 3.26 (s, 3H) 1.83 (d, J = 6.9Hz, 3H). LCMS (method 3): retention time: 1.08 min, m / z 459 [M+H"]. Step C: Preparation of 6-[5-[(15)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]. methyl-aminolethyil- 1,2 4-triazol-1-yllpyridinie-2-carbothioamide (I-38) HaN, Ns / ¢ 3 NA F N, N \ OG Cl To a solution of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile (I-37, 600mg, 1.31mmol, 1eq) in Pyridine (4.8m) was added ammonium sulfide solution in water (2.23ml, 6.54mmol, 5eq). It was stirred for 16h at 25°C. It was diluted with water and extracted three times with ethyl acetate. The combined organic layer was washed brine, dried over anhydrous Na2SOs and concentrated under reduced pressure. It was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to give (I-38) (468mg, 73%). TH NMR (400 MHz, DMSO-d) & ppm 10.06 (brs, 1 H) 9.66 (brs, 1 H) 8.44 (5, 1 H) 8.40 (s, 1 H) 8.41 (d, J =7.4Hz, 2H) 8.27 (5, 1 H) 8.17 (d, J = 2.0Hz, 1 H) 8.05 (d, J = 2.1Hz, 1 H) 7.89 (d, J = 8.0Hz, 1 H) 6.68 (d, J= 7.0Hz, 1 H) 3.26 (s, 3 H) 1.83 (d, J = 7.0Hz, 3 H). 18F NMR (377 MHz, DMSO-d6) & ppm -59.39 (s, 3F). LCMS (method 4): retention time: 1.10 min, m / z 483 [M+H"]. Step D: Preparation of 2-[6-[5-[(18)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yil-methyl-aminolethyil- 1,2 4-triazol-1-yl]-3-pyridyl]-4-(trifluoromethyl)-5H-thiazol-4-ol (I-39) F 7 F \ & = «WM F (| 2N \ LIT AT N, = N \ N Or 0 Cl 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]. methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridinie- 2-carbothioamide (I-38, 100mg, 0.20mmol, 1eq) was dissolved in N,N-Dimethylformamide (2.5ml). To the solution was added 3-Bromo-1,1,1-trifluoroacetone (32.2ul, 0.30mmol, 1.5eq) and it was heated to 60°C for 2h. It was cooled to 25°C and it was diluted with ethyl acetate. It was washed with water and brine, dried over anhydrous Na2SO4 and it was concentrated under reduced pressure. It was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to give (I-39) (103mg, 76%, 90% purity). H NMR (400 MHz, Acetonitrile-d3) & ppm: 8.52 (d, J = 4.4Hz, 1H) 8.32 (ddd J = 12.2, 8.6, 2.3 Hz) 8.07-8.15 (m, 1H) 8.06-8.12 (m, 1H), 8.03(s, 1H) 7.95(dd, J = 8.6, 5.1Hz, 1H) 7.8 (d, J = 2.3Hz, 1H) 7.73 (d, J = 2.2Hz, 1H) 6.76 (t, J = 7.6Hz, 1H) 5.05 (br dd, J = 16.7, 2.6 Hz, 1H) 3.78 (dd, J = 13.0Hz, 10.8Hz, 1H) 3.61(s, 1H) 3.47-3.55 (m, 1H) 3.12 (d, J = 7.5Hz, 3H) 2.09-2.21 (m, 5H) 1.87 (dd, J = 6.9, 1.3Hz, 3H). LCMS (method 4): retention time: 1.17 min, , m / z 604 [M+H*]. Step E: Preparation of 6-chloro-N-methyl-8-(trifluoromethyl)-N-[(18)-1-[2-[5-[4-(trifluoromethyl)thiazol- 2-yl]-2-pyridyl]-1,2.4-triazol-3-yllethyllquinazolin-4-amine (compound P. 142) RF ry =~ W $ / rs VW N, “d N \ OT Cl To a solution of 2-[6-[5-[(1S)-1-[[B-chloro-8-(trifluoromethyl)quinazolin-4-yll-methyl-amino]ethyl]-1,2,4- triazol-1-yl]-3-pyridyl]-4- trifluoromethyl)-5H-thiazol-4-ol (I-39, 100mg, 0.17mmol, 1eq) in Tetrahydrofuran (4ml) was added Triethylamine (58.4pl, 0.41mmol, 2.5eq) and it was cooled to 0 °C. Trifluoroacetic anhydride (118ul, 0.83mmol, 5eq) was added at 0 °C. The reaction mixture was warmed to room temperature and it was stirred for 16h. It was quenched with saturated NaHCOs- solution and it was extracted with EtOAc (2x20ml). The combined organi layer was washed with brine, dried over anhydrous Na2SOs and concentrated under reduced pressure to get gummy mass. The crude material was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to provide desired product P. 142 (47mg, 48% yield). "H NMR (400 MHz, DMSO-a6) 5 ppm 8.65 (s, 1 H) 8.55 (s, 1 H) 8.50 (dd, J = 8.5, 2.3Hz, 1 H) 8.31 (5, 1H) 8.27-8.30 (m, 1 H) 8.06 (5, 1 H) 7.97 (d, J = 8.3Hz 1 H) 7.85 (5, 1 H) 6.65 (br d, J = 6.8Hz, 1 H) 3.10 (s, 3H) 1.88 (d, J = 6.8Hz, 3 H). °F NMR (377 MHz, DMSO-d6) & ppm -59.6(s, 3 F) -62.5 (s, 3 F). LCMS (method 4): retention time: 1.26 min, , m / z 585 [M+H*]. Example 14: Preparation of N-[(18)-1-(2-pyrimidin-2-yl-1,2 4-triazol-3-yl)ethyl]-6.8- bis(trifluoromethyl)-1,2,3-benzotriazin-4-amine (compound P. 145) F NEN H F| i II Ir F z NS N sen WY ANE F Step A: Preparation of 2-amino-3,5-bis(trifluoromethyl)\benzamide (I-40) F NH, © Fi / F z NH, x NE F 2-Amino-3,5-bis(trifluoromethyl)benzonitrile (CAS-No. 473740-86-2, 1.00g, 3.94mmol, 1eq) and potassium carbonate (109mg, 0.79mmol, 0.2eq) were dissolved in Methanol (15ml) and water (2m). While stirring at 25°C urea hydrogen peroxide (1.14g, 11.81mmol, 3eq) was added and stirred for 1h. After that a second batch of urea hydrogen peroxide (1.14g, 11.81mmol, 3eq) was added and stirred for 16h. Sodium metabisulfite (1g) was added and stirred for 5min. It was diluted with ethyl acetate. The solid was filtered off and the filtrate was concentrated under reduced pressure. The crude material was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to provide desired product (I-40) (818mg, 76%). "H NMR (400 MHz, DMSO-a6) 5 ppm 8.22-8.39 (br s, 1H) 8.18 (s, 1H) 7.78 (5, 1H) 7.50-7.70 (br s, 3H). LCMS (method 3): retention time: 0.81 min, , m / z 273 [M+H"]. Step B: Preparation of 6,8-bis(trifluoromethyl)-3H-1,2.3-benzotriazin-4-one (1-41 FNP WH F 1 | F Zz o wy 1 NE F A solution of 2-amino-3,5-bis(trifluoromethyl)benzamide (1-40, 816mg, 3mmol, 1eq) in 1N hydrogen chloride (12m) was stirred for 20min at 0°C. A solution of sodium nitrite (414mg, 6mmol, 2eq) in water (10mi) was added dropwise over 40min. After that it was stirred for 2h at 0°C. 4M sodium hydroxide was added to adjust the pH to 8 and it was vigorously stirred for 15min. The solid was filtered off and fiitrate was acidified to pH 2-3 with HCI. The solid product was filtered off and dried to get (1-41) (382mg, 45%). "H NMR (400 MHz, DMSO-d) 6 ppm 15.56-15.89 (brs, 1H) 8.77 (s, 1H) 8.71 (s, 1H). LCMS (method 3): retention time: 0.92 min, , m / z 284 [M+H*]. Step C: Preparation of tert-butyl N-[(18)-1-(2-pyrimidin-2-yl-1,2 4-triazol-3-yl)ethyllcarbamate (I-42 i) oO SH SAA, H d J Tert-butyl N-[(18)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate (I-33 from example 12, 4.23g, 17.4mmol, 1eq) pyrimidin2-ylhydrazine (2.87g, 26.1mmol, 1.5eq) was mixed together with 1,4-Dioxane (43.5ml) and glacial acetic acid (43.5ml). The mixture was heated to 80°C for 35min. It was concentrated under reduced pressure and purified with flash column chromatography over silica gel (ethyl acetate in cyclohexane) to provide desired product (1-42) (4.03g, 80%). "H NMR (400 MHz, CDCls) 5 ppm 8.89 (d, J = 4.8Hz, 2H) 8.03 (s, 1H) 7.37 (t, J = 5.0Hz, 1H) 5.91- 6.11 (m, 1H) 5.55-5-77 (m, 1H) 1.58 (d, J = 6.6Hz, 3H) 1.35-1.47 (m, OH). LCMS (method 3): retention time: 0.73min, , m / z 291 [M+H*]. Step D: Preparation of [(1S)-1-(2-pyrimidin-2-yl-1,2.4-triazol-3-yl) ethyllammonium;2 2 2-trifluoroacetate 1-43) ~ N\A H. + SNe HT | Tp \ H F tert-butyl N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyljcarbamate (I-42, 36.0g , 86.6mmol, 1eq) was dissolved in Dichloromethane (540ml) and Trifluoroacetic acid (180ml, 2.27mol, 26.2eq) was added. The mixture was stirred at 25°C for 2h. The reaction mixture was concentrated under reduced pressure. Tert-butyl methyl ether (72ml) was added to the crude oil and it was stirred for 5min. The MTBE was decanted off and Acetonitrile (72ml) was added. The product precipitated out, it was filtered off and dried to yield (I-43) (22.39, 83%). "H NMR (400 MHz, DMSO-a6) 5 ppm 9.02 (d, 2H) 8.55-8.75 (brs, 3H) 8.37 (5, 1H) 7.68 (t, 1H) 5.34 (m, 1H) 3.20-4.40 (brs, 1H) 1.63 (d, 3H). LC-MS (method 5): retention time 0.27 min, m / z 191 [M+H"]. Step E: Preparation of N-[(15)-1-(2-pyrimidin-2-yl-1.2.4-triazol-3-ylethvl]-6 8-bis(trifluoromethyl)-1.2.3- benzotriazin-4-amine (compound P. 145) F EN H FL i II I F z NS N Xr Ns ANE F 6,8-bis(trifluoromethyl)-3H-1,2,3-benzotriazin-4-one (I-41, 129mg, 0.45mmol, 1eq), (18)-1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine;2,2,2-trifluoroacetic acid (I-43, 180mg, 0.59mmol, 1.3eq) and N-ethyl-N-isopropyl-propan-2-amine (0.325ml, 1.86mmol, 4.1eq) were dissolved in Dimethylsulfoxide (4.5ml). After stirring for 5min at room temperature benzotriazol-1-yloxy(tripyrrolidin-1- yhphosphonium;hexafluorophosphate (662mg, 1.27mmol, 2.8eq) The resulting mixture was stirred for 16h at room temperature. It was diluted with water (50ml) and it was extracted with EtOAc (3 x 50ml). The combined organic layer was dried over anhydrous Na2SOs and concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded desired product (P. 145) (68mg, 33% yield). "H NMR (400 MHz, DMSO-d) 6 ppm 9.64 (d, J = 7.0Hz, 1 H) 9.34 (5, 1 H) 8.98 (d, J = 4.8Hz, 2 H) 8.61 (s, 1H) 8.17 (s, 1H) 7.64 (t, J = 5.0Hz, 1H) 6.57 (m, 1 H) 1.82 (d, J = 7.0Hz, 3 H). 9F NMR (377 MHz, DMSO-d6) d ppm -58.5 (s, 3 F) -61.2 (s, 3 F). LC-MS (method 3) retention time 0.92 min, m / z 456 [M+H*]. Example 15: Preparation of 3-fluoro-N-methyI-N-[(18)-1-(2-pyrimidin-2-yl-1,2.4-triazol-3-ylJethyl]- 6.8-bis(trifluoromethyl)quinolin-4-amine (compound P.176) '® Tor I! F Ny J 7 Y N F = N \ 2] ay ANE F Step A: Preparation of N-methyl-N-[(15)-1-(2-pyrimidin-2-yl-1.2 4-triazol-3-yhethy[]-6.8- bis(trifluoromethyl)quinolin-4-amine (1-44) ' “NN roar ! Ne JO) Y N F = N \ 2] a ANE F A dry vial was charged with sodium hydride (80 mass%, 13.2mg, 0.33mmol, 1.5eq) and cooled to 0°C. To this was added a solution of N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quinolin-4-amine (P. 5 example 1, 100mg, 0.22mmol, 1eq) in Tetrahydrofuran (0.88mi). After 5min stirring lodomethane (20.8yl, 0.33mmol, 1.5eq) was added and it was stirred at 25°C for 3.5h. It was quenched with sat. NH«Cl-solution (5ml) and diluted with water (20ml). It was extracted with ethyl acetate (3x20ml). The combined organic layer was washed brine, dried over anhydrous Na2SOs and concentrated under reduced pressure. Purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded desired product (I-44) (41mg, 40%). "HNMR (400 MHz, CDCs) 8 ppm 8.65 (d, J = 5.1Hz, 1H) 8.43 (s, 1H) 8.20 (d, J = 1.1Hz, 1H) 8.09 (s, 1H) 8.08 (d, J = 4.8Hz, 2H) 6.93 (t, J = 4.8Hz, 1H) 6.68 (d, J = 5.1Hz, 1H) 6.25 (q, J = 7.0Hz, 1H) 2.88 (s, 3H) 2.08 (d, J = 7.0Hz, 3H). LC-MS (method 3) retention time 1.04 min, m / z 468 [M+H*]. Step B: Preparation of 3-fluoro-N-methyl-N-[(18)-1-(2-pyrimidin-2-yl-1.2 4-triazol-3-ylethyl]-6,8- bis(trifluoromethyl)quinolin-4-amine (compound P.176 '® Tor I! F Ny J 7 Y N F =z N \ 2] ay ANE EF N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine (30mg, 0.064mmol, 1eq) was dissolved in Acetonitrile (321). Selectfluor (23.7mg, 0.064mmol, 1eq) was added and it was stirred at room temperature for 17h. A second batch of Selectfluor (12mg, 0.032mmol, 0.5eq) was added and stired for additional 7h. A third batch of Selectfluor (12mg, 0.032mmol, 0.5eq) was added and stirred for 17h. It was quenched with MeOH, filtered and purified on RP18 silica. P. 176 (18mg, 58% yield). "H NMR (400 MHz, CDCls) 5 ppm 8.68 (d, J = 3.7Hz, 1 H) 8.51 (5, 1 H) 8.15 (5, 3 H) 8.11 (5, 1 H) 8.91 (t, J = 4.8Hz, 1H) 6.03 (q, J = 7.0Hz, 1 H) 3.09 (d, J = 3.7Hz, 3 H) 2.02 (d, J = 7.0Hz, 3 H). 19F NMR (377 MHz, CDCl3) & ppm -60.52(s, 3 F) -62.51(s, 3 F) -133.71 (s, 1 F). LC-MS (method 3) retention time 1.10 min, m / z 487 [M+H*]. Example 16: Preparation of 3-chloro-N-methyl-N-[(18)-1-(2-pyrimidin-2-yl-1,2.4-triazol-3- yl)ethyl]-6.8-bis(trifluoromethyl)quinolin4-amine (P. 181) = "NN LE | EE J, AK ; F ~ 1 x ~ 'g Y C I ANE F Step A: Preparation of 3-chloro-N-methyl-N-[(18)-1-(2-pyrimidin-2-yl-1,2 4-triazol-3-yethyl]-6.8- bis(trifluoromethyl)quinolin-4-amine (compound P. 181) a) “NN I Tp cl {C F F ye | Y F Z NY Xn Nl ANE EF N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-8,8-bis(trifluoromethyl)quinolin-4-amine (I- 44 example 15, 41mg, 0.088mmol, 1eq) was dissolved in Dichloromethane (0.88mi) and cooled to - 19°C. N-Chlorosuccinimide (13mg, 0.096mmol, 1.1eq) was added and stirred for 1h at -19°C. After that it was stirred for 20h at room temperature. Additional N-Chlorosuccinimide (13mg, 0.096mmol, 1.1eq) and Dimethylsulfoxide (31.5ul) were added. After 17h full conversion. It was concentrated under reduced pressure and purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) afforded desired product P.181 (14mg, 32% yield). "H NMR (600 MHz, DMSO-d, 120°C) 5 ppm 8.86 (s, 1H) 8.41 (d, J = 4.7Hz, 2H) 8.24 (s, 1H) 8.13 (s, 1H) 7.24 (t, J = 4.8Hz, 1H) 5.91 (q, J = 7.0Hz, 1H) 3.15 (s, 3H) 1.86 (d, J = 6.9Hz, 3H). LC-MS (method 3) retention time 1.14 min, m / z 502 [M+H*]. Example 17: Preparation of 6-[5-[(15)-1-[[6.8-bis(trifluoromethyl)quinazolin-4-yl]-methyl- aminolethyl]-1,2.4-triazol-1-yl]pyridine-3-carbothioamide (P. 190) HN, VP = Ww Yr F rg. F PN “+ ad Ny \ or “x5 F— —F F Step A: Preparation of 6-[5-[(1S)-1-aminoethyl]-1,2 4-triazol-1-yl]pyridine-3-carbonitrile (I-45) NA lo NA aN Nd Tert-butyl N-[(18)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyllcarbamate (I-34, 75% purity, 13g, 31mmol, 1eq) was dissolved in Dichloromethane (195ml) and Trifluoroacetic acid (78ml, 982mmol, 31.7eq) was added. The mixture was stirred at 25°C for 1h. The reaction mixture was concentrated under reduced pressure. Dichloromethane (195ml) was added to the crude oil and it was basified with saturated Na2COa- solution. The aqueous layer was extracted with dichloromethane (2x200ml). The combined organic layer was dried over anhydrous Na2SOs and concentrated under reduced pressure to give a white solid. This was washed TBME and was dried under reduced pressure to give (I-45) (7g, 87%, 88% purity). "H NMR (400 MHz, DMSO-a6) 5 ppm 9.06 (s, 1H) 8.55 (d, 1H) 8.23 (s, 1H) 8.06 (d, 1H) 4.67-4.87 (m, 1H) 1.47 d, 3H). Step B: Preparation of 6-[5-[(18)-1-[[6,8-bis(trifluoromethyhquinazolin-4-yllaminolethyl]-1.2.4-triazol-1- yllpyridine-3-carbonitrile (1-46) F | JI H I FY WH z N oN ROR" . Fie: wf F 4-chloro-8,8-bis(trifluoromethyl)quinazoline (1-8 example 2, 4.0g, 13.3mmol, 1eq) was dissolved in acetonitrile (40ml). 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (I-45, 85% purity, 3.35g, 13.3mmol, 1eq) and cesium carbonate (8.67g, 26.6mmol, 2eq) were added and it was stirred at 25°C for 16h. The reaction mixture was poured on ice-water and it was extracted with ethyl acetate (3x50ml). The combined organic layer was dried over anhydrous Na2SQ4 and concentrated under reduced pressure followed by purification by flash chromatography over silica gel (ethyl acetate in cyclohexane) to afford desired product (1-46) (5.1g, 80%). "H NMR (400 MHz, DMSO-d) 6 ppm 9.47 (d, 1H) 9.27 (s, 1H) 9.04 (s, 1H) 8.58 (d, 1H) 8.44 (s, 1H) 8.36 (5, 1H) 8.21 (s, 1H) 8.09 (d, 1H) 6.42 (quin., 1H) 1.77 (d, 3H). LC-MS (method 5) retention time 1.59 min, m / z 479 [M+H*]. Step C: Preparation of 6-[5-[(1S)-1-[[6.8-bis(trifluoromethyl)quinazolin-4-yll-methyl-amino]ethyl]-1.2 4- triazol-1-yl]pyridine-3-carbonitrile (1-47 = Ww FE NANN Fd | 7 N, F Zr N \ Sean" Ne F A sealable tube was charged with 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-ylJamino]ethyi]- 1,2,4-triazol-1-yllpyridine-3-carbontitrile (I-46, 294mg, 0.61mmol, 1eq), acetonitrile (4.92mi), cesium carbonate (601mg, 1.84mmol, 3eq) and iodomethane (77.3yl, 1.23mmol, 2eq). The vial was sealed and heated to 50°C for 16h. After cooling to 25°C it was diluted with water (10mi) and it was extracted with ethyl acetate (3x10ml). The combined organics were washed with brine, dried over anhydrous NazSOs« and concentrated under reduced pressure. It was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) and afforded desired product (I-47) (250mg, 83%). "H NMR (400 MHz, CDCls) 5 ppm 8.55 (s, 1H) 8.35 (d, J =5.9 Hz, 2H) 8.24 (s, 1H) 8.11 - 8.20 (m, 2H) 8.03(s, 1H) 6.88 (q, J = 6.97Hz, 1H) 1.96 (d, J = 6.97Hz, 3H). 19F NMR (377 MHz, CDCl) 5 ppm -61.33 (s, 3F) -62.39 (s, 3F). LC-MS (method 3) retention time 1.11 min, m / z 493 [M+H"]. Step D: Preparation of 6-[5-[(15)-1-[[6,8-bis(trifluoromethyl)auinazolin-4-yll-methyl-aminolethyil-1.2.4- triazol-1-yllpyridine-3-carbothioamide (P. 190) HN ¥* = w ENP Fd r N F = N \ SRR NE F 6-[5-[(18)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile (I-47, 300mg, 0.61mmol, 1eq) was dissolved in Pyridine (2.4ml) and ammonium sulfide solution (20mass%, 1.04ml, 3.05mmol, 5eq) was added. The reaction mixture was stirred at 25°C for 16h. It was diluted with water and it was extracted with ethyl acetate (4 times). The combined organic layer was washed with brine, dried over anhydrous NazSOs4 and concentrated under reduced pressure. It was purified by flash chromatography over silica gel (ethyl acetate in cyclohexane) to give (P. 190) (78mg, 24%). "H NMR (400 MHz, DMSO-a6) 5 ppm 10.04 (br s, 1H) 9.65 (brs, 1H) 8.55 (s, 1H) 8.27 - 8.41 (m, 5H) 7.91 (d, J = 8.44Hz, 1H) 6.76 (br d, J=6.85Hz, 1H). °F NMR (377 MHz, DMSO-d6) 5 ppm -59.74 (s, 3F) -60.75 (s, 3F). LC-MS (method 4) retention time 1.12 min, m / z 528 [M+H*]. STRUCTURE [M+H] Method Table P: Examples of compounds of formula | Entry IUPAC name STRUCTURE ! (measured) LX N-[(18)-1-(2-pyrimidin- AN 455 3 N-[(18)-1-(2-pyrimidin- 2.yl-1,2,4-triazol-3- ~ ylethyll-6,8- fF ha. bis(trifluoromethyl)quina ! A N 2zolin-4-amine NY N F F 448 3 2zolin-4-amine F “| ~ x F——F P.2 6,7,8-trichloro-N-methyl- a2 pin iby 0, / ,e-nchloro-N-metnyl- N-[1-(3-pyrimidin-2- 2 amine ylpyrazin-2- \ Hay N yhethyllquinazolin-4- al 1 NA amine d $) Ci Cl P.3 6,78 trichloro-N-[1-[3- mn, 423 3 : triazol-2-y| in-2- (triazol-2-y)pyrazin- nN 6,7,8-trichloro-N-[1-[3- (triazol-2-yl)pyrazin-2- nN N fo NPN TW yllethyllquinazolin-4- i amine a NA H i or ne 1 p.4 N-[1-(5-bromo-2- 547-549 (Br3 pyrimidin-2-yl-1,2,4- ay my pattern) bis(triiuorometnyi)quina Fr WJ 1 zolin-4-amine x Ng N-[1-(5-bromo-2- pyrimidin-2-y-1,2,4- my triazol-3-yl)ethyll-N- i NN New methyl-6,8- | Ap bis(trifluoromethyl)quina F y N zolin-4-amine Ny FF 8 455 3 To [p-5 N-[(18)-1-(2-pyrimidin- PN N-[(1S)-1-(2-pyrimidin- = 2411 2 4triazok3- A H &-yl-1,£,4-U1d201-0- a: n yhethyl}-6,8- FNP he bis(trifluoromethyl)quino >! 1 AUN lin-4-amine HS H / £7 Ne P6 6-[5[1-6,8- 117 507 3 1 bis(trifluoromethyl)quina AN zolin-4-yl]-ethyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- TALI wh Tare he Em anne. La Zzolin-4-yil-ethyl- J aminolethyll-1,2,4- triazol-1-yl]pyridine-3- & carbonitrile ef NN ¥ SN [4 F F F P7 eisn-6e- Lo 113 sz 3 bis(trifluoromethyl)quina zolin-4-yl]- {methoxymethyl)amino] (meth oxymethyl)amino] $ ethyl]-1,2,4-triazol-1- 1 yllpyridine-3-carbonitrile g_ / f NN OY F N NY F F ? F ba 6-5 8-[5-[1-[benzyl-[6,8- 1.21 569 3 bis(trifluoromethyl)quina N zolin-4-ylJamino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile nD ef YN oO N ? ar, Yn F P9 [6,8 1.10 504 3 | [6.8- 1.10 504 3 bis trifluoromethyl)quina N zolin-4-yl]-[1-[2-(5- cyano-2-pyridyl)-1,2,4- triazol-3- yllethyllcyanamide F orn 9 F Ny | NY =r F benzyl N-[6,8- 1.18 613 3 bis(trifluoromethylquina N zolin-4-yl]-N-[1-[2-(5- cyano-2-pyridyl)-1,2,4- triazol-3- yllethyllcarbamate or TFN hg) H pyrimidin-2-ylpyrazin-2- 4 yhethyl]-8- NPN Ny (trifluoromethoxy)quinaz ~~ F, 1 olin-4-amine AOC F H Rar Br P12 8-bromo-N-[1-(3- PN 0.92 492-494 (Br3 nd F O=DIOMO=IN=| 1={o= V.dc B / ILGIG pyrimidin-2-ylpyrazin-2- a) pattern) yhethyl]-6- Zz , Ss (trifluoromethoxy)quinaz g, ) olin-4-amine Ny 3 F xX, P.1 3 8-bromo-N-[1-[3-(triazol- mm 1.00 481-483 (Br3 ©-RIOMO=IN={ 1-]o-{U1az0l- mm UU 401-409 2-yl)pyrazin-2-yllethyl]- Cal N N pattern) 2yl, In-2-yljetnyl}- N, 1} = yheyaEn yllethyl] NN Nye = rt aE HE | (trifluoromethoxy)quinaz Br olin-4-amine H [] Cc 1 fo , ps4 6-bromo-N-[1-[3-(triazol- mA 0.99 481-483 (Br3 2-yl)pyrazin-2-yljethyl]- is NN pattern) olin-4-amine FY L § H 2-yl)pyrazin-2-yljethyl]- ~ NN 8- ' F (trifluoromethoxy)quinaz X ) oo, olin-4-amine F H 9 Br 6-[5-[1-[methyl-[2- Nn 120 507 3 155 - methyl-6,8- mM 158 bis(trifluoromethyl)quina zolin-4-ylJamino]ethyl]- 6-[5-[1-[methyl-[2- Nn 120 methyl-6,8- hy bis(trifiuoromethyl)quina zolin-4-ylJamino]ethyl]- = 3 1,2,4-triazol-1- NN yilpyridine-3-carbonitrile f, NN N N / Yr i F 455 3 192 - 4 P.16 N-[1-(2-pyrimidin-2-yl- i Pe A idol oralN matey dy N-[1-(2-pyrimidin-2-yl- 097 1.2. 4-triazol-3-ylethyll- ~\ 1,2,4-triazol-3-yl)ethyl]- = 3 194 6,8- ce won NON NSN 1,2,4-triazol-3-yl)ethyl]- a 6,8- ZN he bis(trifluoromethylquina F | AY zolin-4-amine H pa 1 “Ne Pa 7 B-[5-[(1S)-1-[[8-Chloro-6- 6-[5-[(1S)-1-[[8-chloro-6- nN 099 445 3 (trifluoromethyl)quinazol 1 in-4-ylJamino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile F pe 8-chloro-N-[(18)-1-(2- 143 421 5 pyrimidin-2-yl-1.2,4- = triazol-3-yl)ethyl]-6- 8-chloro-N-[(18)-1-(2- = pyrimidin-2-yl-1,2,4- I) triazol-3-yl)ethyl]-6- het (trifluoromethyl)quinazol a NPN Nr in-4-amine \ N Hong F fF F P.19 6-[5-[(1S)-1-[[8-chloro-6- (trifluoromethyl)quinazol » in-4-yll-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- NPSN carbonitrile 6- ol NPN & C ) NY nd F F 7 A Tv h Xx / r a F F {P.20 8-chloro-N-methyl-N- = [(18)-1-(2-pyrimidin-2- yl-1,2,4-triazol-3- NON 8-chloro-N-methyl-N- — [(18)-1-(2-pyrimidin-2- ) yl-1,2,4-triazol-3- NPN NN yhethyl}-6- c AA (trifluoromethyl)quinazol YL in-4-amine £ £ p21 8-[5-[(19)-1-{[6-chloro-8- (trifluoromethylquinazol in-4-yl]-methyl- amino]ethyl}-1,2,4- triazol-1-yllpyridine-3- o dd a aminojethyl]-1,2,4- <) triazol-1-ylpyridine-3- ~ NU carbonitrile f F NN , YY NG ! p22 6-[5-[(1S)-1-[[6-chloro-8- N (trifluoromethyl)quinazol in-4-yllamino]ethyl]- 1,2,4-triazol-1- I]pyridine-3-carbonitrile yllpyridi i Cf NPN yilpynaine-s-carboninie n NPN NN Sel Hoa 1 iP.23 6-chloro-N-methyl-N- AN [(1S)-1-(2-pyrimidin-2- {(18)-1-(2-pyrimidin-2- A) yi-1,2,4-triazol-3- ¢ VO he yhethyl]-8- (rifluoromethyl)quinazol YY in-4-amine NY 1 6-chloro-N-[(18)-1-(2- pyrimidin-2-yl-1,2,4- ~~ triazol-3-yl)ethyl}-8- fF, NN Ny-n I 1 RW ai Ee Li 1 v (trifluoromethyl)quinazol in-4-amine ¥ 16 I a VL p25 2-chloro-N-[1-(2- 2-chloro-N-[1-(2- 1.09 pyrimidin-2-yl-1,2 4- a rN Ne pyrimidin-2-yl-1,2,4- i triazol-3yDethyl[68- _ £ NZ w YC) bistrifluoromethydauina ~~. Lil 1 7 zolin-4-amine F 1 °T W P.26 N-methyl-N-[(1S)-1-(2- bis(trifluoromethyl)quina zolin-4-amine ~ ef yo YY p27 N-methyl-N-[1-(2- N-methyl-N-[1-(2- pyrimidin-2-yl-1,2,4- ~~ triazol-3-yhethyl]-6,8- Ff NPN NN pyhimin-c=yi-1,«,%= gy A tiazol-3-y)ethyl]-6,8- FNP yn bistrifiuoromethyl)quina F: M zolin-4-amine FY he P.28 B-[5-[1-[[6,8- Ny 1 ' bis(trifluoromethyl)quina nn zolin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-ylpyridine-3- triazol-1-yllpyridi °c NPSN carbonitrile F N 1.11 | I A 1) . NSN NN N F——F F 6,8-dibromo-N-[1-(2- 0.85 473-478 3 pyrimidin-2-yl-1,2 4- A (dibromo triazol-3- H N pattern) yhethyllquinazolin-4- . N amine Br P.29 6,8-dibromo-N-[1-(2- pyrimidin-2-yl-1,2,4- A triazol-3- H N ylethyllquinazolin-4- amine 8r x 3 Ns \ P30 &-[5-1-[68- Br - 6-[5-[1-[(6,8- 0.98 499-504 3 dibromoquinazolin-4- A (dibromo yhamino]ethyl}-1,2,4- J 8 J pattern) triazol-1-yl]pyridine-3- a N carbonitrile P.30 6-[5-[1-[(6,8- 0.98 499-504 3 dibromoquinazolin-4- A (dibromo yhamino]ethyl}-1,2,4- H N pattern) triazol-1-yl]pyridine-3- carbonitrile Br \ NaN p ==, \ Pat 6-bromo-8- mm 0.89 463-465 (Br3 amine Fk J H Are preps UA TE (difluoromethoxy)-N-[1- ~ NON [3-(triazol-2-yl)pyrazin- yo 2-yllethyl]quinazolin-4- No Z amine ’ H J Re: Br p32 e-bomo-8- oN 080 474-476 (Br3 ©-PIOMmo-e- u.ou 474-470 (difluoromethoxy)-N-[1- i pattern) (3-pyrimidin-2-ylpyrazin- NSN, H (difluoromethoxy)-N-[1- % (3-pyrimidin-2-ylpyrazin- NSN 2-y)ethyllquinazolin-4- ¢ or amine 0) H x Rr Br Pas 6-bromo-N-[1-[3-(triazol- mM 1.07 465-467 (Br4 6-bromo-N-[1-[3-(triazol- 1.07 465-487 2-ypyrazin-2-yllethyl]- JN patter) in-4-amine F 1° I H 2-yl)pyrazin-2-yljethyl]- NA 8 FN? Ma (trifluoromethylquinazol © y in-4-amine F 7 H | NN Br IP.34 8-bromo-N-[1-[3-(triazol- 1.04 465-467 4 : 2-yl)pyrazin-2-yljethyl]- JN F 8-bromo-N-[1-[3-(triazol- 2-yl)pyrazin-2-yljethyl]- \ 6- NTN (trifluoromethyl)quinazol ge y in-4-amine ¥~ WN nS F- F F 8-chloro-N-[1-[3-(triazol- 421 2-yhpyrazin-2-yllethyl]- KAR 2-yl)pyrazin-2-yllethyl]- NN 6- (trifluoromethyl)quinazol ¢, in-4-amine ZN H | F F P.36 8-chloro-N- ~ 505 (cyclopropylmethyl)-2- oo ~=N 8-chloro-N- ~ (cyclopropylmethyl)-2- ~N methoxy-N-[1-(2- a NM N pyrimidin-2-yl-1,2,4- 1] triaanl 2 yhathull & a AMAL triazol-3-yl)ethyl]-6- {trifluoromethylquinazol 475-479 (trifluoromethyl)quinazol NZ i in-4-amine Y Ny F t F par 6,8-dibromo-N-[1-[3- 7 B,e-aibromo=N={1-[3- 1 473-419 (triazol-2-yl)pyrazin-2- IN (dibromo ang YE Ine NSN OY en A] il in-4- NTN yllethyl]quinazolin-4 B Toa ¥ N pattern) yheuiylQuinazotii-4- Tr in , 1 amine Br J NA Zz ae x Br 486-490 3s 6,8-dibromo-N-[1-(3- 9, 0-UIDTOMO=IN-{ 1-{o- A400-49V pyrimidin-2-ylpyrazin-2- 7 (dibromo yhethyllquinazolin-4- NSN N pattern) A NTR amine Io a U4 Br H | % Br P39 6-chloro-N-[1-[3-(triazok- m 421 B-CNIOro-iN-{1-|o-(nazol- mM 2-yl)pyrazin-2-yljethyl]- NN in-4-amine F 1° J H sR TRERTE FUERA 8- FON? WC (trifluoromethylquinazol ) in-4-amine F z H | NS Cl IP.40 6-chloro-N-[1-(2- 6-chloro-N-[1-(2- 421 pyrimidin-2-yl-1,2,4- 5 Ct 6-chloro-N-[1-(2- pyrimidin-2-yl-1,2,4- '® triazol-3-yl)ethyl]-8- F NPN on (trifluoromethylquinazol Y N in-4-amine F H 0 N a - 6-[5-[1-[6-chloro-8- 445 5 (trifluoromethylquinazol WN in-4-yllamino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile | A F J om NY 'P.42 6-[5-[1-[[8-bromo-6- N 489-491 (Br4 i (trifluoromethyl)quinazol 1H pattern) in-4-yllamino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile F = ® z NN Br ) N, hd FF F IP.43 8-chloro-N-[1-(2- 422 4 : pyrimidin-2-yl-1,2,4- AN 8-chloro-N-[1-(2- pyrimidin-2-yl-1,2 4- = triazol-3-ylethyl]-6- yn (trifluoromethylquinazol ¢ ! N in-4-amine WN N H No F £ IP.44 6-bromo-N-[1-(2- 465-467 (Br4 ¥ pyrimidin-2-yl-1,2,4- = pattern) al fe Ie r— pyrimidin-2-yl-1,2,4- = triazol-3-yl)ethyl]-8- PONFN ou (trifluoromethyl)quinazol F J) N, in-4-amine F H N Br Br 6-[5-[1-[[8-chloro-6- 445 5 (trifluoromethyl)quinazol N in-4-yllamino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile [= J NN Y c Fork F ¥F p.4s 8-bromo-2-chloro-N- 553-555 (Br4 (cyclopropylmethyl)-N- a li pattern) 8-bromo-2-chloro-N- (cyclopropylmethy-N- 1 = [1-(2-pyrimidin-2-yl- z Ny-n 1,2,4-triazol-3-yDethyl- gy A WN | 6- Tir Vv (trifluoromethyl)quinazol (trifluoromethyl)quinazol x NY in-4-amine £ wv P47 8-bromo-N-{1-2- = 465-467 (Br4 i ‘P.47 8-bromo-N-[1-(2- : pyrimidin-2-yl-1,2,4- 3 triazol-3-y)ethyl-6- z yn (trifluoromethyl)quinazol gg y N in-4-amine Nr N H No F [p48 2,8-dichioro-N-[1-(2- a AN 2,8-dichloro-N-[1-(2- pyrimidin-2-yl-1,2,4- 3 i triazol-3-y)ethyl-6- N he (trifluoromethyl)quinazol ¢ J N, in-4-amine Ne N H Ns F- F F F pp.49 2,8-dichloro-N- 2,8-dichloro-N- 509-513 4 (cyclopropylmethyl)-N- ¢ YN (dichloro 6- rr Vv (trifluoromethyl)quinazol in-4-amine ~ 2,8-dichloro-N- 509-513 (cyclopropylmethyl)-N- a = (dichloro [1-(2-pyrimidin-2-yl- pe pattern) 1,2 4-triazol-3-yhethyll- ci N 6- NY N (trifluoromethyl)quinazol NY in-4-amine F F v 5 F P50 6-[5-[1-16,7.8- 105 447 9 1 trichloroquinazolin-4- A ylhamino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile 53 C | [*= ". rl N Y c | PP.51 8-bromo-2-chloro-N-[1 1.05 499-503 (Cl4 iP. -Dromo-2-chloro-N-[1- 3 = { Cooney ETL Ay Ce 8-bromo-2-chloro-N-[1- 1.05 499-503 (2-pyrimidin-2-yl-1,2,4- + Br triazol-3-yl)ethyl]-6- 7 pattern) (trifluoromethyl)quinazol Nh SHMEMEM JMR o (trifluoromethyl)quinazol A in-4-amine Nr £ NN F Ci Br IP.52 6-[5-[1-[[6-bromo-8- 6-[5-[1-[[6-bromo-8- n 109 503-505 (Br3 149 - (trifluoromethyl)quinazol n pattern) 152 in-4-yl]-methyl- aminolethyl]-1,2,4- triazol-1-yl]pyridine-3- ATEN. carbonitrile . F NN FN Tr Br [P53 B[5-[(1R)-1-[18.6- bis(trifluoromethyl)quina zolin-4-yl]-methyl- aminolethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile F N ; f 1 F F F bis(trifluoromethyl)quina mn 142 zolin-4-yl]-methyl- aminojethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile 1.10 i “3 (JN NN f Ym F——F F Pp.ss N-[1-[3-(triazol-1- 1.08 456 3 : yl)pyrazin-2-yllethyl]- N \ N-[1-[3-(triazol-1- yl)pyrazin-2-yllethyl]- vo) 6,8- F = ' N bis(trifluoromethyl)quina F zolin-4-amine F 3 $ X F | ; PP.56 N-[1-[3-(triazol-2- N-[1-[3-(triazol-2- A 1.09 456 3 189 - ylpyrazin-2-yllethyl]- pa J % 191 N-[1-[3-(triazol-2- yl)pyrazin-2-yljethyl]- 3 N 8,8 tf AL bis(trifluoromethyl)quina ZN zolin-4-amine H NJ F F P.57 6-[5-[1-[16.8- y 11 43 3 I bis(trifluoromethyl)quina zolin-4-ylJ-methyl- aminolethyl}-1,2,4- triazol-1-yl]pyridine-3- carbonitrile i rs NN or N F F F F .58 N-methyl-N-[1-(2- a 101 489 3 pyrimidin-2-yl-1,2,4- N-methyl-N-[1-(2- 7 pyrimidin-2-yl-1,2,4- li triazol-3-y)ethyl]-6,8- r -n bis(trifluoromethylquina F ! WN zolin-4-amine 1 N FF P59 6-[5-[1-12,6,8- y 120 547 3 1 tris(trifluoromethylquina n zolin-4-ylJamino]ethyl]- F F tris(trifluoromethyl)quina y zolin-4-ylJamino]ethy]- F 1,2,4-triazol-1- F—F = hd) Lo N yl]pyridine-3-carbonitrile F. F | Ne H NZ F——F F peo 6-[5-[1-[[2-methyl-6,8- N18 404 3 bis(trifluoromethylquina n zolin-4-ylJamino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile F 1.16 i “I > . NAN NN f YN F- F F pst 6-5-{1-[(6.8- B-[5-[1-[[6,8- N 1.07 479 3 bis(trifluoromethyl)quina nN zolin-4-ylJamino]ethyl]- 1,2, 4-triazol-1- yl]pyridine-3-carbonitrile F eS NN 0 F Cn FF F p62 6-[5-[1-[[8- N 0.93 411 3 ! 6-[5-[1-[[8- 093 411 3 (trifluoromethyl)quinazol A» in-4-yllamino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile H J P63 6-[5-[1-[[6-bromo-8- N 489-491 (Bra (trifluoromethylquinazol nm pattern) in-4-yllamino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile rf YEN $V Rp Fo; Br P64 B5{1-[6 6-[5-[1-[[6- 411 3 (trifluoromethyl)quinazol aN in-4-ylJamino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile NS H AAS F Ps 6-[5-[1-(6,8- ) 6-[5-[1-[(6,8- N 411-415 3 dichloroguinazolin-4- nw (dichloro yhamino]ethyl]-1,2,4- I pattern) triazol-1-yl]pyridine-3- ZA carbonitrile ON J § ’ N Cl hey . ~l cl ps6 6,8-dichloro-N-methyl- 6,8-dichloro-N-methyl- = 401-405 N-[1-(2-pyrimidin-2-y- oO > 1,2,4-triazol-3- 1.2440az003- NEN TN pattern) 8,8-dichloro-N-methyl- N-[1-(2-pyrimidin-2-yl- 3 1,2,4-triazol-3- Nu yhethylquinazolin-4- C ! Nel amine i \ N NY i 386-390 ! IP.67 6,8-dichloro-N-[1-(2- ~N Cl pyrimidin-2-yl-1,2,4- Md. (dichloro triazol-3- ~ ¢) pattern) yhethyllquinolin-4-amine ¢j, oN = J a 2387-391 1 P.68 6,8-dichloro-N-[1-(2- 6,8-dichloro-N-[1-(2 ~=N =N pyrimidin-2-yl-1,2,4- oN (dichloro triazol-3- > N NN 7 \ pattern) ANS aa Nis A Cy 1] 1 =, amine Tr I NH Cl 2385 3 peo N-[1-[2-(2-pyridy))-1,2,4- lin-1-amine N-[1-[2-(2-pyridyl)-1,2,4- — triazol-3-ylethyl]-5- (trifluoromethyl)isoquino E Zz \ lin-1-amine ) 8 H i N NS EL Va [P.70 7-bromo-N-[1-(2- NL 396-398 (Br3 / =Dromo=IN={ 1-(£= pyrimidin-2-yl-1,2,4- = triazol-3- Ny ybethyllisoquinolin-1- § WN amine N HN {P.71 8-bromo-N-methyl-N-[1- 8-bromo-N-methyl-N-[1- 481 4 (2-pyrimidin-2-yl-1,2,4- m0 8-bromo-N-methyl-N-[1- (2-pyrimidin-2-yl-1,2,4- my triazol-3-yl)ethyl]-6- -. LT 8-bromo-N-methyl-N-[1- (2-pyrimidin-2-yk-1,2,4- my triazol-3-yl)ethyl]-6- =N (trifluoromethyl)quinazol a in-4-amine Nr “§ NZ F EE LJ rr IN Nt F p72 6-[3-[1-[[8-chloro-6- 5 6-[3-[1-[[8-chloro-6- 511 4 (trifluoromethyl)quinazol N in-4-yl]- (cyclopropylmethyl)amin o]ethyllpyrazin-2- yl]pyridine-3-carbonitrile nn @ joes P.73 6-[3-[1-[[8-bromo-6- N (trifluoromethylquinazol "nm in-4-yl]- (cyclopropylmethyl)amin F 6-[3-[1-[[8-bromo-6- N (trifluoromethyl)quinazol ip in-4-yl}- (cyclopropylmethyl)amin N o]ethyl]pyrazin-2- ZN yl]pyridine-3-carbonitrile \ Br NA N NJ : + F 'P.74 6-[3-[1-[[6-bromo-8- (trifluoromethyl)quinazol in-4-yl]- (cyclopropylmethyl)amin ney (cyclopropylmethyl)amin i x o]ethyl]pyrazin-2- E Zz _ yllpyridine-3-carbonitrile F. 1 24a Qe Br > Y he Br > ps N-(cyclopropylmethyl)- 7 IN-(CyClopropyimetnyl)- mM N-[1-[3-(triazol-2- nN £5 zolin-4-amine N-(cyclopropylmethyl)- N-[1-[3-(triazol-2- Jd “ yDpyrazin-2-yllethyll- ~~ F C 6,8 2 bis(trifluoromethyl)quina F Cl i zolin-4-amine > fv p.78 8-chloro-N- O=CHIOTO=IN= \ (cyclopropylmethyl)-N- as ci % in-4-amine 8-chloro-N- \ (cyclopropylmethyl)-N- N N [1-[3-(triazol-2- NTN N ylpyrazin-2-yllethyl]-6- Ci 3 NA (trifluoromethylquinazol I it in-4-amine x A ££ F p77 6-chloro-N- ©-Chioro-iN- 7 \ (cyclopropylmethyl)-N- gn & " (trifluoromethyl)quinazol in-4-amine (cyclopropylmethyl)-N- NN [1-[3-(triazol-2- ef | N yhpyrazin-2-yllethyll-8- ANA (trifluoromethyl)quinazol 1 of) in-4-amine ~ X Cl P.78 6-bromo-N- \ {cyclopropylmethyl)-N- PR ¥ 1 (trifluoromethyl)quinazol in-4-amine (cyclopropylmethyl)-N- NN [1-[3-(triazol-2- ff | AL yl)pyrazin-2-yllethyl]-8- Zz (trifluoromethyl)quinazol 1 $$) in-4-amine > D Br P.79 6-bromo-N-[1-{2-(5- {trifluoromethylquinazol in-4-amine iLO INL =a bromo-2-pyridyl)-1,2,4- triazol-3-yllethyl]-8- = 3 (trifluoromethylquinazol RX in-4-amine FENN N 0 \ F F N Ae : nN FLY H ps0 6-bromo-N- O=DIromo-=iN= ZZ (cyclopropylmethyi)-N- 7, lS] imidin-2- NS [-@pyrimidin2- ys NSA L1I=(e-pyhimidin-<= Call voviazin2-yhethyie. Eo Yd (trifluoromethyl)quinazol FT II oN in-4-amine fey oY % A d Wi Br P.81 8-chloro-N- O=CHIOTO=IN= (cyclopropylmethyl)-N- , [1-(3-pyrimidin-2- VN Ny Tr 8 a SS F 8-chloro-N- (cyclopropylmethyl)-N- , [1-(3-pyrimidin-2- / Ny ylpyrazin-2-yl)ethyl]-6- a 1 {trifluoromethyhquinazol WNP in-4-amine nS Pv F iP.82 cyclopropyl-{4-[methyl- [(19)-1-(2-pyrimidin-2- in-6-yljlmethanone cyclopropyi-{4-[methyl- = [(1S)-1-(2-pyrimidin-2- O yl-1,2,4-triazol-3- . - ylethyllamino]-8- A (rifluoromethylquinazol YY n in-8-ylJmethanone NY o P.83 N-[1-(2-pyrimidin-2-yl- 1.08 454 3 1 1,2 4-triazol-3-ylethyl]- eS or 57 bis(trifluoromethyl)isoqui Ia " nolin-1-amine ce | N PF i IAD p.g4 N-methyl-N-[(15)-1-(2- N-methyl-N-[(18)-1-(2- 108 502 3 pyrimidin-2-yl-1.2.4- ~N triazol-3-yl)ethyl]-8- (trifluoromethyl)-6- (trifluoromethylsulfanyl) FY | ow quinazolin-4-amine x 090 465 3 [p85 N-{1-(3-pyrimidin-2- INL T=(o-PYTITIdITN=2= ylpyrazin-2-yl)ethyl]-6,8- 2 bis(trifluoromethylquino F NTN ' Ny hai: alanine © dy ellie ~ 1 lin-4-amine rd v 1 : H F ! yt oh F | " | IP.86 6-iodo-N-methyl-N- 75-80 i 1(1S)-1-(2-pyrimidin-2- A) i (trifluoromethylquinazol in-4-amine B-iodo-N-methyl-N- = [(19)-1-(2-pyrimidin-2- yl-1,2,4-triazol-3- QQ yhethyl}-8- F UN (trifluoromethyl)quinazol YY in-4-amine p87 6-i0do-N-[(1S)-1-(2- 6-iodo-N-[(15)-1-(2- = 096 513 3 252- pyrimidin-2-yl-1 2,4 la) 255 in-4-amine r hid nT N B-iodo-N-[(15)-1-(2- = pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]-8- i) (trifluoromethyl)quinazol k A N in-4-amine YN P.88 N-methyl-N-[(1S)-1-(2- 104 469 3 N-methyl-N-[(18)-1-(2- gr pyrimidin-2-yl-1.2,4- ~~ tiazol3yDethyi 68 ) Ny bis(trifluoromethylquino , lin-4-amine C YN F—F P.89 N-[1-[2-(5- wu 111 547-549 Bra bromopyrimidin-2-yl)- pattern) 1,2,4-triazol-3-yljethyl]- A SE TAREE FUE i! 1 N-methyl-6,8- Ny bis(trifluoromethyl)quina F h zolin-4-amine N av 1 P.oo 6-chloro-8- 6-chloro-8- 0.83 433 3 i r= (difluoromethoxy)-N- la) methyl-N-[(1S)-1-(2- O=-CNioro-o- (difluoromethoxy)-N- ~ methyl-N-[(1S)-1-(2- ~n iH pyrimidin-2-yl-1,2,4- E | : triazol-3- YY yhethyllquinazolin-4- NY amine a Pot 8-chloro-6- © em 8-chloro-6- 0.83 433 3 (difluoromethoxy)-N- IY methyl-N-[(1S)-1-(2- pyrimidin-2-yl-1,2,4- 8-chloro-6- (difluoromethoxy)-N- ~~ methyl-N-[(1S)-1-(2- ZN he pyrimidin-2-yl-1,2,4- |] . triazol-3- c YY Ny yhethyllquinazolin-4- NY amine ~° pe N-[1-[2-(5- 1.07 533-535 (Br3 bromopyrimidin-2-yl)- pattern) 1,2,4-triazol-3-yl]ethyl]- = \ FIN I wn 1,£,4-Nazoi-s-yljetnylj- HR] 85 NSN "SN bis(trifluoromethyhquina ¢_ Ff | zolin-4-amine N f NY ON 1 Ne P.93 6-chloro-8- = 419-421 (CI3 (difluoromethoxy)-N- la) pattern) Cl (difluoromethoxy)-N- 0 [(18)-1-(2-pyrimidin-2- a] en yl-1,2,4-triazol-3- 3 ) + yhethyllquinazolin-4- T NY Ny i Ho wy amine Cl Ip.o4 8-chloro-6- 419-421 (CI3 (difluoromethoxy)-N- 7 pattern) ame WY H (difluoromethoxy)-N- 0 [(18)-1-(2-pyrimidin-2- ca] Ny yl-1,2,4-triazol-3- 1] 1 yhethyllquinazolin-4- g NY amine Ho Ny Cc nN he [P.95 8-iodo-N-[(18)-1-(2- 513 3 ! pyrimidin-2-yl-1,2,4- ~N in-4-amine Lo) H Al MN fF i F [P.96 8-bromo-N-[1-(3- 476-478 (Br4 [P96 8-bromo-N-1-3- AN 476-478 O=DIOITIO=IN=| 1={o= S4 / 0-470 pyrimidin-2-ylpyrazin-2- A pattern) yhethyl]-6- Na oN BE NZSN Ny pyrimidin-2-ylpyrazin-2- I~ n yhethyl]-6- x (trifluoromethyl)quinazol NPN hd in-4-amine br NA H nS F Tc F .97 8-bromo-N-methyl-N-[1- + p-97 8-bromo-N-methyl-N-[1 AN 490-492 (Br4 O=DIVMO=-IN=-THiCtl yi=iN=| 1= R / IU-GIL (3-pyrimidin-2-ylpyrazin- a) pattern) 2-ylethyl]-8- (trifluoromethylquinazol 8-bromo-N-methyl-N-[1- (3-pyrimidin-2-ylpyrazin- I) 2-ylethyl]-6- z 3 -N (trifluoromethyl)quinazol Br i; in-4-amine NA x F P.98 6-bromo-N-methyl-N-[1- 490-492 (Br5 (3-pyrimidin-2-ylpyrazin- A pattern) 2-yhethyl-8- <=yyeuiyip=o= F r™ (trifluoromethylquinazol Fwy ¥ Fo 4 in-4-amine FIFI WN Br Lo Ip.99 8-bromo-N- a 530-532 (Br5 O=DIOMO=IN= POU=00<4 (cyclopropylmethyl)-N- 3 pattern) 8-bromo-N- (cyclopropylmethyi)-N- 3 [1-(3-pyrimidin-2- z Yio ylpyrazin-2-yl)ethyl]-6- Br (trifluoromethyl)quinazol NA in-4-amine N : Vv Ppa 00 8-chloro-N-methyl-N-[1- A 446 5 V O=CHHOTO=IN=ITICLIYI=IN={ I= (3-pyrimidin-2-ylpyrazin- , 2-yhethyl}-6- i VSN Ny RS pl J TUF LOOT Ia Wy hctadli 3 2-yhethyl]-6- | Ny (trifluoromethyl)quinazol a i in-4-amine NP NJ F- F F {P.101 8-chloro-N-[1-(3- 1 8-chloro-N-[1-(3- 432 5 pyrimidin-2-ylpyrazin-2- 3 yhethyl]-6- NS N Rr rer pra abt res iis sai val NN pyrimidin-2-ylpyrazin-2- ~ ylethyl]-6- Ny ~N (trifluoromethyl)quinazol N N in-4-amine a a H | XN F P.1028-chloro-N-methyl-N-[1- 2 8-chloro-N-methyl-N-[1- mm 435 5 [3-(triazol-2-yl)pyrazin- oo N N ; NL 7in. oN [3-(triazol-2-yl)pyrazin- N 2-ylJethyl]-6- NTN Ny (trifluoromethyl)quinazol Cli J NA in-4-amine 1 J x F- F F 3N-methyl-N-[1-3- a= 470 4 (triazol-2-yl)pyrazin-2- Fd \ 3 N-methyl-N-[1-[3- (triazol-2-yl)pyrazin-2- ON ylethyl]-6,8- rf NPN bis(trifluoromethyl)quina J A zolin-4-amine F ) F——F P.104 8-bromo-N-methyl-N-[1- 479-481 (Br4 [3-(triazol-2-yl)pyrazin- JN, pattern) F 4 8-bromo-N-methyl-N-[1- [3-(triazol-2-yl)pyrazin- IN 2-yllethyl]-6- NPN (trifluoromethyl)quinazol Br. Z in-4-amine 1 It > F- F F Pi 05 8-bromo-N-methyl-N-[1- mm 479-481 (Bra 2 ©-Dromo-N-metnyi-IN-|1- 7 \ 4 / 9-401 [3-(triazol-2-yl)pyrazin- a iY % pattern) in-4-amine FI UH 1 [3-(triazol-2-yl)pyrazin- NN (trifluoromethylquinazol Z in-4-amine 1 of) 3 Br 456 4 {P106 N-[1-(3-pyrimidin-2- O IN-| 1=(e-pyTimidin-«- ylpyrazin-2-yl)ethyl]-6,8- [a bis(rifluoromethyhquina WP, MeN WioUuvivinictinyyyultia F Cali 1 zolin-4-amine Fs N* N 1 a) tS Cyt OG LN a H J F- F PAOTN-methy N13 J - £ IN=NEINYI=IN=L T={o= pyrimidin-2-ylpyrazin-2- pyrimidin-2-ylpyrazin-2- ZN yhethyl}-6,8- z | NN bis(trifluoromethyl)quina F F Y zolin-4-amine fF YN a 1 F P.108 N-(cyclopropylmethyl)- AN 1.20 QINT\LYLIUPITUP yITTICLU YI )= N-[1-(3-pyrimidin-2- , Ipyrazin-2-ylethyl-6 8- 3 vipyrazin-2-yhethyll68- yoy Nye bis(trifluoromethyl)quina zolin-4-amine IAL I F p-1 09 N-[1-[3-[5- 9 N-[1-[3-[5- 1.21 (difluoromethoxy)-2- £ pyridyl]pyrazin-2- yllethyl]-6,8- bis(trifluoromethyl)quina zolin-4-amine Ged PAON-{1-{3-[5- 0 N-[1-[3-[5- 1.21 (difluoromethoxy)-2- £ pyridyl]pyrazin-2- yllethyl]-N-methyl-8,8- bis(trifluoromethyl)quina zolin-4-amine P.1118-bromo-N-[1-[3-[5- 1.15 : (difluoromethoxy)-2- £ pyridyllpyrazin-2- yllethyl]-6- (trifluoromethyl)quinazol in-4-amine H P.112 8-chloro-N-[1-[3-[5- £ c MTUITIVTUTINTL ETT (difluoromethoxy)-2- L pyridyllpyrazin-2- o° OF yllethyl]-N-methyl-6- (trifluoromethyl)quinazol in-4-amine F ol | 3 NON ZN Cl F F IP.1138-chloro-N-[1-[3-[5- 2 ATMEL TIL F (difluoromethoxy)-2- 1 pyridyl]pyrazin-2- yllethyl]-6- {trifluoromethyl)quinazol in-4-amine H ned he pi 148-bromo-N-{1-[3-[5- ; (difluoromethoxy)-2- i pyridyllpyrazin-2- oF yllethyl]-N-methyl-6- (trifluoromethylquinazol in-4-amine ae F P.1156-[3-[1-[[6,8- | bis(trifluoromethyl)quina zolin-4- yllamino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile ed F 66-[3-[1-[[6,8- % 505 4 bis(trifluoromethyl)quina p 20lin-4-ylJ-methyl- 1 amino]ethyl]pyrazin-2- yllpyridine-3-carbonitrile " aa QO ed P.117 6-[3-[1-[[8-bromo-6- 7 6-[3-[1-[[8-bromo-6- 500-502 (Br5 (trifluoromethyl)quinazol N pattern) in-4- { B=[o= 1=||O-Dromo-o- (trifluoromethyl)quinazol § in-4- yllamino]ethyl]pyrazin-2- Nn yllpyridine-3-carbonitrile ! P i | Br WN Ho NJ 1 y) H ny Wt * Rs he P.1186-[3-[1-[[6-chloro-8- N 8 6-[3-[1-[[6-chloro-8- 456 5 (trifluoromethyhquinazol N in-4- yllamino]ethyl]pyrazin-2- yllpyridine-3-carbonitrile NPN H HARE F NN NT PP H NJ | P.119.6-{3[1-{(6-bromo-8- i 500-502 (Bré MM LT UY MEV MVMIME (trifluoromethyl)quinazol i pattern) in-4- yllamino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile 9) P.1206-chloro-N-[1-[3-[5- E 1.69 gliadin Toll "uid "uli (difluoromethoxy)-2- pyridyllpyrazin-2- 0 yl]ethyl]-8- (trifluoromethyl)quinazol in-4-amine rn os Mg Y " nA 1 P.121 6-{3-[1-[[8-chloro-6- " 1.53 PML TUM HEA N (trifluoromethyl)quinazol 1H in-4- (trifluoromethyl)quinazol Ih in-4- yllamino]ethyl]pyrazin-2- NN yllpyridine-3-carbonitrile | N 2 Zr a NA H NJ F F £ F p12 6-[3-[1-[[8-chloro-6- 2 6-[3-[1-[[8-chloro-6- N 1.55 (trifluoromethylquinazol "w in-4-yl]-methyl- 2 6-[3-[1-[[8-chloro-6- N (trifluoromethyl)quinazol in-4-yl]-methyl- amino]ethyl]pyrazin-2- i yl]pyridine-3-carbonitrile _ 1 ! i F E F p123 6-chloro-N-[1-[3-[5- 1.20 (difluoromethoxy)-2- k pyridyl]pyrazin-2- yllethyl]-N-methyl-8- (trifluoromethyl)quinazol in-4-amine OF P.1246-[3-[1-[[8-bromo-6- N 514-516 (Br5 (trifluoromethyl)quinazol "w pattern) in-4-yll-methyl- amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile F zol i" a N | F F F P.125 6-[3-[1-[[6-bromo-8- 5 6-[3-[1-[[6-bromo-8- 514-516 (Br5 (trifluoromethyl)quinazol N pattern) in-4-yl]-methyl- amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile p28 6-[3-{1-(16.8- 6 6-[3-[1-[[6,8- 545 4 bis(trifluoromethylquina N zolin-4-yl]- (cyclopropylmethyl)amin olethyllpyrazin-2- yl]pyridine-3-carbonitrile F o Na J > [P-1276-bromo-N-methyl-N-{1- AN 479-481 (Br Br 7 6-bromo-N-methyl-N-[1- (2-pyrimidin-2-yl-1,2,4- \ triazol-3-yl)ethyl]-8- NPN = N (trifluoromethyl)quinazol F. F in-4-amine Ne \ N [4 Br P.1286-[5-[(1S)-1-[[6-chioro-8- (trifluoromethyhquinazol N in-4-yl]-ethyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- triazol-1-ylJpy! CF NPN LALO 1 =Y HRY T= \ UN carbonitrile eS NAN ‘ MH Yn NY 1 P.1296-chloro-N-methyl-N-[1- _ YJ B-Chioro-N-metnyl-N-{1- \ [3-(triazol-2-yl)pyrazin- = NN in-4-amine FI HI 1 [3-(triazol-2-yl)pyrazin- N, N 2-yllethyl]-8- ‘ St N (trifluoromethyl)quinazol ANA in-4-amine 1 Q) RD Cl P-1308-chloro-N-[1-(3- V O=CIHOTO=IN= 1={O= pyrimidin-2-ylpyrazin-2- fn yhethyl-8- NaN (trifluoromethyl)quinazol ¢_ Ff N= No “y in-4-ami 7 in-4-amine Ps OE Ci P-1 3186-chloro-N- 1 0-COro-iN- ZF (cyclopropylmethyl)-N- 3, [-@pyrimidin2- omy Nye LI=(empyiiiinditi=e= NN” 1 Jipyrazin-2-yhethyll-8- Ff LR 1 (trifluoromethyl)quinazol FCT Y in-4-amine _ S) R FI LIE ) wv Cl > Ppt 326-chloro-N-methyl-N-[1- (3-pyrimidin-2-ylpyrazin- nd a 26-chloro-N-methyl-N-[1- (3-pyrimidin-2-ylpyrazin- oO, 2-ylethyl]-8- ENF , Ny (trifluoromethyl)quinazol F: NA a ~ in-4-amine F N 19 Cl P.1336-bromo-N-[1-(3- ~~ 161 480-482 Br5 193. | fn) pyrimidin-2-ylpyrazin-2- Ld 0 pattern) 195 yethylke- wy, Ny (trifluoromethyl)quinazol in-4-amine H a) FY ; My RE Br p1 346-[5-[(1R)-1-{[6,8- 46-[5-[(1R)-1-[[6,8- 0.94 497 3 bis(trifuoromethyheinnol ? in-4-ylJaminojethyll- rf Lh 1,2,4-triazol-1- yl]pyridine-3- carboxamide Pt 356-[5-[(1R)-1-[[6.8- 56-[5-[(1R)-1-[[6,8- 1.01 480 3 bis(trifuoromethyheinnol | £ N* indylaminoletnyle NLL ML 1,2,4-triazol-1- yl]pyridine-3-carbonitrile P.136 N-{1-(2-pyrimidin-2-yI- 6 N-[1-(2-pyrimidin-2-yl- = 0.91 455 3 1,2,4-triazol-3-yl)ethyl]- - = H 1,2,4-triazol-3-yl)ethyl]- 50 6.8: : ha. bistrifluoromethyl)cinnol F: | ANA in-4-amine H ON F i ! 187 6-chloro-N-methyl-N- 1.06 50227 4 77-79 | Piiiuiaipiiig Neen 7 6-chloro-N-methyl-N- Ne 1.06 502.27 4 77-79 {(18)-1-[2-[5-(1H- AEN tetrazol-5-yl)-2-pyridyl]- Ch 1,2,4-triazol-3-yllethyl]- 8- (trifluoromethyl)quinazol in-4-amine Kd 84-[[(15)-1-(-pyrimidin- ~~ 1.10 47963 4 = 203- 2-yl-1,2 4-triazol-3- _N la 205 O 4-{{{1o)-1-(&-PYyHITNairn- 2-yl-1,2,4-triazol-3- ~ yhethyljamino}-6,8- FNP . Nn bis(trifiuoromethyl)quino F: AUR line-3-carbonitrile HS H 4 Pe Pp 39 4-[[(15)-1-[2-(5-cyano-2- 9 4-[[(18)-1-[2-(5-cyano-2- Ny 118 S032 4 204 - pyridyD)-1,2,4-triazol-3- mn 206 yllethyllJamino]-6,8- bis(trifluoromethyl)quino line-3-carbonitrile - Ho » n YY Ho Ny he p-140 4-methyl-[(19)-1-(2- a 113 40363 4 84-86 | 04-[methyl-[(18)-1-(2- 1.13 49363 4 84-86 oyrimidin-2-yl-1,2,4- IN line-3-carbonitrile Ua-meinyl-({1o)-1-(&- oyrimidin-2-yl-1,2,4- ~ triazol-3-yhethyllaminol- _ f NZ \ 5h 6,8- F : : N bis trifluoromethyl)quino YL line-3-carbonitrile £7 Ie P41 4-[[(18)-1-[2-(5-cyano-2- 88-90 14-[[(18)-1-[2-(5-cyano-2- Ny 119 517.28 4 88-90 pyridyD)-1.2 4-triazol-3- n yl]ethyl]-methyl-amino]- 6,8 bis(trifluoromethyl)quino {line-3-carbonitrile P.142 6-chloro-N-methyl-8- 1.26 EAB mor on ALA Th BAAR FB (trifluoromethyl)thiazol- a, (trifluoromethyl)-N-[(1S)- ; FF 1-[2-[5-[4- (trifluoromethylythiazol- / ARHHMATTR Ly eRert gq 1 2-yl]-2-pyridyil-1,2,4- Ns triazol-3- i yllethyl]quinazolin-4- amine Cl iI “I FENTON NN F. ] . Cl 1.19 {P.143 6-chloro-N-methyl-N- nigel; ill < WTMTIVTTINTTTIA LL Y TN [(18)-1-[2-(5-thiazol-2- 1 yl-2-pyridyl)-1,2,4- triazol-3-yllethyl]-8- (trifluoromethyl)quinazol in-4-amine ¥ i YY Cl 0.90 pa 44 6-bromo-8-chloro-N- 4 0-Dromo-o-Cnioro-N- methyl-N-[1-(3- a) metnyl-N-[1-(3- Iu pyrimidin-2-ylpyrazin-2- NPN \ NN ylethyllquinazolin-4- a j) amine ’ If Ny Br p14 N-[(1S)-1-(2-pyrimidin- 5 N-[(18)-1-(2-pyrimidin- 0.92 2-yl-1,2,4-triazol-3- Lo = 1,2,3-benzotriazin-4- La 1 nT nN amine AY Lyla TL YR A yhethyl-6,8- Ms pel bis(trifluoromethyl)- F Uo. 8 1,2,3-benzotriazin-4- HB amine “Ne Ppt 46 6-cyclopropyl-N-methyl- f Soll duis air ABRs, 6 6-cyclopropyl-N-methyl- 0.97 N-[(18)-1-(2-pyrimidin- AN in-4-amine 6 8-cyclopropyl-N-methyl- = N-[(1S)-1-(2-pyrimidin- 2-yl-1,2,4-triazol-3- F NZ QQ yhethyl}-8- F AUN (trifluoromethylquinazol YL in-4-amine A A in-4-amine indie Antiid tlied 3 Aiibuiibbingt’ Juli N-[(18)-1-(2-pyrimidin- = 2-yl-1,2 4-triazol-3- NPN on yhethyl]-6- An (trifluoromethyl)quinazol YN in-4-amine J poder PB F 1.15 p.148 6-[3-(1S)-1-[[6-i0do-8- wT TT ELMIRA (trifluoromethyl)quinazol ll in-d-vll-methvl- in-4-yl]-methyl- amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile Yea SPARE MEI ; F NN YY" , Nn 7 OL 149 6-[3-[(18)-1-[8-iod0-6- " 9 6-[3-[(1S)-1-[[8-iod0-6- 1.15 (trifluoromethyl)quinazol N in-4-yl]-methyl- amino]ethyl]pyrazin-2- N=4-yl]-metiyl- amino]ethyl]pyrazin-2- “3 yllpyridine-3-carbonitrile N | : F 1 F IP.1506-chloro-N-methyl-N- 1.16 [(19)-1-[2-[5-(1,2,4- N Q oxadiazol-3-yl)-2- pyridyl]-1,2,4-triazol-3- yljethyl]-8- HYTYE bye, ariliasiize= yilethyil-8- 2 (trifluoromethyl)quinazol FONPON NN in-4-amine k Y Ne road 1 P.151 6-chloro-N-methyl-8- 1.27 570.25 75-77 © EAB mor on ALA Th BAAR FB i 16-chloro-N-methyl-8- 1.27 570.25 (trifluoromethyD-N-[(1S)- FF 1-[2-[5-[5- (trifluoromethyl)-1,2,4- 79 oxadiazol-3-yl]-2- N_N pyridyl]-1,2,4-triazol-3- yllethyl]quinazolin-4- amine Cl I “I FENTON NN F. ] . Cl 2 8-chloro-N-[1-[2-[5- 1.52 486.1 240 - (difluoromethoxy)-2- oF 242 pyridyl]-1,2,4-triazol-3- yllethyl]-6- (trifluoromethyl)quinazol in-4-amine 1.52 F NN ol 1 c N F—F F IP.1538-chloro-N-[1-[2-5- 3 8-chloro-N-[1-[2-[5- 1.53 500.2 102 - (difluoromethoxy)-2- of 104 pyridyl]-1,2 4-triazol-3- yllethyl]-N-methyl-6- {trifluoromethyl)quinazol in-4-amine 4.53 F NN ol NN ZN Cr NN 7) F- F F I} i P.154 8-bromo-N-[1-[2-[5- 155 546.1 75-77 | C77 (difluoromethoxy)-2- f | pyridyl]-1,2,4-triazol-3- yllethyl]-N-methyl-6- (trifluoromethylquinazol in-4-amine 1.55 A, ol ~y Q ore F——F bis trifiuoromethyhquina 5 wi, 185 Zolin-4-yl-methyl- oT amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carboxamide J YH Ip 56 6-[5-[(1S)-1-[[6-chloro-8- 1.01 492.26 4 223 - ? (trifluoromethyl)quinazol Lg , 225 in-4-yl]-methyl- 1 amino]ethyl]-1,2,4- triazol-1-yl]-N "-hydroxy- pyridine-3- carboxamidine rn ov Ci Pa 576-5-[(15)-1-[[6,8- 76-[5-[(18)-1-[[6,8- 1.03 497.27 4 bis(trifluoromethylquina Oy nn, zolin-4-ylJamino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3- carboxamide ed P.158 6-[5-[1-[(8-bromo-6- 8 8-[5-[1-[(8-bromo-6- | 0.98 455 3 chloro-quinazolin-4- q NN ylhamino]ethyl]-1,2,4- ZX H triazol-1-yl]pyridine-3- carbonitrile P.158 6-[5-[1-[(8-bromo-6- 3% ! chloro-quinazolin-4- A yhamino]ethyl}-1,2,4- H N triazol-1-yl]pyridine-3- carbonitrile Br % Nar \) \ p1 59 6-bromo-8-chloro-N-[1- Be 0.8 9 6-bromo-8-chloro-N-[1- 0.81 431 3 (2-pyrimidin-2-yl-1,2,4- & NN triazol-3- ZN HM yhethyllquinazolin-4- amine 16-[3-[(1S)-1-[[8-iodo-6- 548 3 (trifluoromethylquinazol N in-4- yllamino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile A P.162 6-[3-[(1S)-1-[[6-iod0-8- 548 3 4 (trifluoromethyl)quinazol N in-4- 2 6-[3-[(15)-1-[[6-1000-8- (trifluoromethyl)quinazol a in-4- yllamino]ethyl]pyrazin-2- 2) yllpyridine-3-carbonitrile NE N 1 N NAN H NS EN) [2 nS P.1636-[5-((18)-1-{[6- uy 515 3 {cyclopropyl(difluoro)me thyl]-8- (trifluoromethylquinazol in-4-yl]-methyl- amino]ethyl]-1,2,4- FF So I Tb (trifluoromethyl)quinazol = in-4-yl]-methyl- N aminojethyl}-1,2,4- EF NN N triazol-1-yl]pyridine-3- Z N carbonitrile “OO vi P.164N-[(18)-1-[2-(5- = 547-549 (Br3 N-methyl-6,8- TINIE E TAN MENTE bromopyrimidin-2-yl)- pattern) 1,2,4-triazol-3-yl]ethyl]- = ) N-methy!-6,8- x NN bis(trifluoromethvhauina ¢. fF NN . F bromopyrimidin-2Z-yl)- i 1,2,4-triazol-3-yl]ethyl]- = ) N-methyl-6,8- 2 Nn bis(trifluoromethyl)quina ¢. F = ' XL zolin-4-amine ¥ YOY N F: F F 56,8-dichloro-7-fluoro-N- 091 419 3 145 - methyl-N-[1-(2- iN my 225 Cl 56,8-dichloro-7-fluoro-N- methyl-N-[1-(2- 2 pyrimidin-2-yl-1,2,4- ? Ne triazol-3- c J N yhethyllquinazolin-4- YN N amine NY Cl bp 66 6,8-dichloro-7-fluoro-N- 6 6,8-dichloro-7-fluoro-N- 0.86 4053 215 - [1-(2-pyrimidin-2-yl- Nn my 155 4 WON LN Cl 6 6,8-dichloro-7-fluoro-N- [1-(2-pyrimidin-2-yl- 2 1,2,4-triazol-3- 7 Ne yhethyllquinazolin-4- ¢ y N amine Ny N NZ Cl IP.167 methyl N-[6,8- 7 methyl N-[6,8- 1.08 537 3 bis(trifluoromethyl)quina N zolin-4-yl]-N-[1-[2-(5- cyano-2-pyridyl)-1,2,4- triazol-3- yllethyllcarbamate F NPN . F N F—1—F ? B F p16 8-[5-[(19)-1-[[6,8- 8 6-[5-[(15)-1-[[6,8- 1.15 507 3 bis(trifluoromethyl)quina oN zolin-4-yl]-ethyl- aminolethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile F oF 0 F Yn F—F EF [P.1696-[5-[(15)-1-[(6.8- N 1.14 523 3 ! bis(trifluoromethyl)quina zolin-4-yl]- (methoxymethyl)amino] ethyl]-1,2,4-triazol-1- yl]pyridine-3-carbonitrile r Q | OL TF ? i P.1706-5-[(1S)-1-[16- 106 493 3 1 (cyclopropanecarbonyl)- N 8- (trifluoromethyl)quinazol in-4-yl]-methyl- (trifluoromethyhquinazol = ) in-4-yl]-methyl- A aminojethyll-1,2,4- ; NPN } triazol-1-yl]pyridine-3- yh . " carbonitrile 1 As 0 |P.171 8-bromo-6-chloro-N-[1- 1 8-bromo-6-chloro-N-[1- | 0.84 431 3 205 - (@-pyrimidin-2-yl-1.2,4- q oN 238 triazol-3- ZN) H ylethyllquinazolin-4- amine PATH 8-bromo-6-chloro-N-[1- | i (2-pyrimidin-2-yl-1,2,4- 2 triazol-3- H MN ylethyllquinazolin-4- amine Br 1 Ne \ y = iP 72 8-bromo-6-chloro-N- a 2 8-bromo-6-chloro-N- | 0.89 445 3 methyl-N-[1-(2- q NN pyrimidin-2-yl-1,2,4- ZN + triazol-3- yhethyllquinazolin-4- Br amine 3 8-bromo-6-chloro-N-[1- [mm] 0.93 431 3 175 - [3-(triazol-2-yl)pyrazin- Nal NUN 200 amine H pt 73 8-bromo-6-chloro-N-[1- — [3-(triazol-2-yl)pyrazin- Zz N,N 2-ylethyl]quinazolin-4- 1 1 amine Br oy Hon Ci 1.00 445 3 105 - pa 74 8-bromo-6-chloro-N- 4 8-bromo-6-chloro-N- 1.00 445 3 105 - methyl-N-[1-[3-(triazol- PY IN 166 4 8-bromo-6-chloro-N- methyl-N-[1-[3-(triazol- W { “\ 2-yl)pyrazin-2- N N yllethyllquinazolin-4- fags amine 1 nd XN, 1 P.1756-[3-[(15)-1-[[6,8- N bis(trifluoromethylquina N zolin-4-yl]-methyl- amino]ethyl]-5-methyl- pyrazin-2-yl]pyridine-3- carbonitrile fF PA 76 3-fluoro-N-methyl-N- lin-4-amine W = HUI Lm N= Ly re [(1S)-1-(2-pyrimidin-2- ~ yi-1,2,4-triazol-3- e NF, yn yhethyl}-6,8- F \ UK bis(trifluoromethylquino ¢ i lin-4-amine FF F F pa 776-[5-{(1S)-1-[[6- cyclopropyl-8- (trifluoromethyl)quinazol in-4-yl]-methyl- amino]ethyl}-1,2,4- A 76-[5-[(15)-1-[[6- N cyclopropyl-8- y (trifluoromethylquinazol in-4-yll-methyl- A aminojethyl]-1,2,4- tiazol-1-yllpyridine-3- g_ F N° . YN carbonitrile ‘ XN YY IP. 78 6-bromo-8-chloro-N-[1- © ©-Dromo-o-cnioro-iN-{1- (3-pyrimidin-2-ylpyrazin- 3 (3-pyrimidin-2-ylpyrazin- ru 2-ylethyllquinazolin-4- \ NN amine Cl ! NA " J XS Br [p79 8-bromo-N-methyl-N-[1- 9 O-DIOMO-IN-rmetiyi=in-1 1= \ : 3 1 \ [3-(triazol-2-yl)pyrazin- ~ Natholl 2 NPN NC N 2-yllethyl]-6- [3-(triazol-2-yl)pyrazin- N,N 2-yllethyl}-6- NN a (trifluoromethoxy)quinaz NAA olin-4-amine B | N <= yleuylj=o= 1 i 3 I (trifluoromethoxy)quinaz Bf N olin-4-amine J C 1 fo eX, 06-bromo-8- ~~ m= 093 (difluoromethoxy)-N- oe ¥ % yllethyllquinazolin-4- : amine (difluoromethoxy)-N- =z Ne N methyl-N-[1-[3-(triazol- No 2-yl)pyrazin-2- ig AL yllethyllquinazolin-4- F J amine Ar Br p.181 3-chloro-N-methyl-N- 1 3-chloro-N-methyl-N- 1.14 1(18)-1-(2-pyrimidin-2- I. AN lin-4-amine Lhd ah all liod Lh Lah al [(18)-1-(2-pyrimidin-2- ~ yl-1,24-triazol-3- e NOC, NyN yhethyl}-6,8- F bic UR bis(trifluoromethyl)quino ~~ ¢ i lin-4-amine FF F 0.90 I Ci p.1838-bromo-6-chioro-N-[1- pn 0.84 9 O-RIOMO-0-CHIOTO=-IN-11= (3-pyrimidin-2-ylpyrazin- [a H 2-y)ethyllquinazolin-4- Z Ny oN amine Be |} My ae Cl I 84 6-[5-[(1)-1-[[6-iod0-8- 1.10 (trifluoromethyl)quinazol N in-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- Lee TY Up JT IMI carbonitrile FN" POE P.1858-bromo-N-[1-[2-(5- i 4959 (Br © O=UTUTTIU=IN] I=[am(v= F AIT L fluoro-2-pyridyl)-1,2,4- ’ pattern) triazol-3-yllethyl]-N- methyl-6- triazol-3-yllethyl]-N- r= methyl-6- \ 4 (trifluoromethyl)quinazol , N in-4-amine Br, N i 4 N F F Et F P.186 8-bromo-N-[1-[2-(5- E 483.9 (Br WA CEA fl iingingiodll ‘ma fluoro-2-pyridyl)-1,2,4- F pattern) triazol-3-ylethyl]-6- = (trifluoromethyl)quinazol N 4 in-4-amine NTN N c ) gd a F P.1 87 6-chloro-N-[1-[2-(5- fF 452.3 4A TIO) fmm] Ew mln fluoro-2-pyridyl)-1,2,4- F triazol-3-yllethyl]-N- 3 methyl-8- N Naz0l=o-yljetiyif-IN- anil. methyl-8- $i (trifluoromethyl)quinazol A&E in-4-amine ay F \ ON y / 1 8 6-bromo-N-[1-[2-(5- 496.3 (Br fluoro-2-pyridyl)-1,2,4- F pattern) p1 88 6-bromo-N-[1-[2-(5- fluoro-2-pyridyl)-1,2,¢ triazol-3-yllethyl]-N- methyl-8- Hazul=o=yljCuUlylj=IN= Fe methyl-8- $d (trifluoromethyl)quinazol ¢ F in-4-amine N Ae Hn BRIN F { P.189 N-[1-[2-(5-fluoro-2- pyridy))-1,2,4-triazol-3- F yilethyl}-N-methyl-6 &- Q bis(trifluoromethyl)quina / zolin-4-amine Fp NPN N\A "A 06-[5-[(1S)-1-[[6,8- 1.12 bis(trifluoromethyl)quina HN zolin-4-yl]-methyl- amino]ethyl]-1,2,4- F 06-[5-[(1S)-1-[(6,8- " 112 bis(trifluoromethyl)quina 2 S zolin-4-yl}-methyl- aminojethyl]-1,2,4- 2 triazol-1-yl]pyridine-3- FE NPN N\_N carbothioamide F. | AN F YY N F F F {P.191 6-[5-[(15)-1-[[6-chloro-8- 16-[5-[(1S)-1-[[6-chloro-8- 1.10 (trifluoromethylquinazol Sq NH, in-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbothioamide vA [4] She ¢ v YY pa 92N-[1-{2-(5- 2 N-[1-[2-[5- 1.61 (difluoromethoxy)-2- f pyridyl]-1,2,4-triazol-3- ylethyl]-N-methyl-6,8- bis(trifluoromethyl)quina . zolin-4-amine F 1.61 F i NN) rf ¥ =N F——F F P.193N-[1-[2-[5- ge 159 NL Te pa F (difluoromethoxy)-2- 4 pyridyl]-1,2,4-triazol-3- yllethyl]-6,8- bis(trifluoromethyl)quina zolin-4-amine ny F- ’ wv fF 4 6-bromo-N-[1-[2-[5- ¢ 1.19 54574 (difluoromethoxy)-2- l pyridyl]-1,2,4-triazol-3- yllethyl]-N-methyl-8- yllethyl]-N-methyl-8- N (trifluoromethyl)quinazol ef N in-4-amine y Ne F 'N 4 Br p1 95 6-bromo-N-[1-[2-[5- 56-bromo-N-[1-[2-[5- + 1.59 4300 (difluoromethoxy)-2- gal pyridyl]-1,2 4-triazol-3- yl...

Claims

CLAIMS 1. A compound of the formula | "NA3 R3 po ~ A2_ | Tog 0 EN | | Ad _ AS R1 gp R2a wherein: Ai, Az and As are, independently from each other, N or CRy; As and As are, independently from each other, N or CRy; R4a R4 1 ANA R5 Qis Qe? or QP Ri is hydrogen, C1-Cealkyl, C1-Cecyanoalkyl, aminocarbonylC1-Cealkyl, hydroxycarbonylCi-Cealkyl, C1- Cenitroalkyl, trimethylsilaneC1-Csalkyl, C1-Caalkoxy-C1-Cealkyl, C1—Cshaloalkyl, Cz-Cealkenyl, Cz- Cshaloalkenyl, C2-Cealkynyl, C2-Cshaloalkynyl, Cs-CscycloalkylCi-Czalkyl-, Ca-CacycloalkylCi-Caalkyl- wherein the Cs-Cscycloalkyl group is substituted with 1 or 2 halogen atoms, oxetan-3-yl-CHz-, Ci- Cealkylcarbonyl, C1-Csalkoxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, benzyl or benzyl substituted with 1 to 3 substituents independently selected from halogen, C1-Csalkoxy and Ci- Cehaloalkyl; Rza and Ras are each independently selected from hydrogen, C1-Caalkyl, C1-Cshaloalkyl, C1- Cshaloalkylsulfanyl, Ci- Csalkoxy, C1- Cshaloalkoxy, halogen, NOz, SFs, CN, C(O)NHz, C(O)OH, C(S)NHz, Ca-Cscycloalkyl, Ca-Cscycloalkyl substituted with one to three substituents independently selected from Rx, Ca-Cecycloalkylcarbonyl, phenyl, phenyl substituted with one to three substituents independently selected from Rx, heteroaryl, heteroaryl substituted with one to three substituents independently selected from Rx, ORs, piperidin-2-one-1-yl, piperidin-2-one-1-yl substituted with one to two substituents independently selected from Rx, pyridin-2-one-1-yl, pyridin-2-one-1-yl substituted with one to two substituents independently selected from Rx, azetidin-1-yl, azetidin-1-yl substituted with one to two substituents independently selected from Rx pyrrolidin-1-yl, pyrrolidin-1-yl substituted with one to two substituents independently selected from Rx, Ca-CscycloalkylCi-Csalkyl, Ca-CecycloalkylCi- Caalkyl substituted with one to two substituents independently selected from R;; Cs-CscycloalkyICi- Caalkoxy, Ca-CscycloalkylCi-Caalkoxy substituted with one to two substituents independently selected from Rx, C1-Cscyanoalkyl, C1-Cscyanoalkoxy, Ci-Caalkylsulfanyl, C1-Csalkylsulfanyl substituted with one to three substituents independently selected from Rx, C1-Csalkylsulfonyl, C1-Caalkylsulfonyl substituted with one to three substituents independently selected from Rx, C1-Caalkylsulfinyl, and Ci- Caalkylsulfinyl substituted with one to three substituents independently selected from Ry; Ra is C1-Caalkyl or C4-Cahaloalkyl; Rs is pyridine, pyrimidine, pyrazine or pyridazine; or Rs is pyridine, pyrimidine, pyrazine or pyridazine each of which, independently of each other, is substituted with one to two substituents independently selected from C1-Csalkyl, C1-Cshaloalkyl, C1- Csalkoxy, Cs-Cacycloalkyl, halo, hydroxyl, CN, Ci-Cshaloalkoxy, C2-Cshaloalkenyloxy, C2- Cshaloalkynyloxy, Cs-Cshalocycloalkoxy. NH2C(O)-, NH2C(S)-, (OH)N=C(NHz)- and a 5-membered heteroaryl ring optionally substituted by 1 to 3 substituents independently selected from halogen, Ci- Caalkyl, Ci-Cshaloalkyl, C1-Caalkoxy and Ci-Cshaloalkoxy; Rusa is pyridine, pyrimidine, pyrazine, pyridazine; or Rua is pyridine, pyrimidine, pyrazine or pyridazine each of which, independently of each other, is substituted with one to three substituents independently selected from C1-Caalkyl, C1-Cshaloalkyl, Ci- Caalkoxy, Ca-Cacycloalkyl, halogen, hydroxyl, cyano, and Ci-Cshaloakoxy; or Rasa is Y1,Y2, Y3, and Y4 Rip, Rio rd \ “N” nn Y1 Y2 Y3 Y4 wherein, R'sa, R's, and R's, independently of each other and independently of Y1 to Y4, are selected from hydrogen, halogen, CN, C+-Csalkyl, C1-Cshaloalkyl, Cs-Cscycloalkyl, C1-Csalkoxy, and Ci- Cshaloalkoxy; Rs is hydrogen, C1-Caalkyl, Ci-Cshaloalkyl, Cs-Cscycloalkyl, Ci-Csalkoxy, Cs-CsalkoxyC(O)-, (Ci- Csalkoxy)2CH-, halogen, CN, NH2C(O), amino (i.e NHz), (C1-Caalkyl)amino, di(C1-Csalkyl)amino, hydroxy, Ca-Cshalocycloalkyl, Cs-Cacyanocycloalkyl, C2-Csalkenyl, Cz-Cshaloalkenyl, Cz-Csalkynyl, Cz Cshaloalkynyl, Ci-Cshaloalkylsulfanyl, C1-Cshaloalkylsulfinyl, C1-Cshaloalkylsulfonyl, C1- Caalkylsulfanyl, C1-Csalkylsulfinyl, C1-Caalkylsulfonyl, C1-Caalkoxy-C1-Caalkyl, C1-Caalkoxy-Ci- Caalkoxy-C1-Caalkyl, (C1-Caalkyl)sulfonylamino, (C1-Csalkyl)sulfonyl(Ci-Csalkylyamino, (C:- Caalkyl)NHC(O), (C1-Caalkyl)z2NC(O), (Ci-Cscycloalky)NHC(O), (C1-Cacycloalkyl)(Ci-Csalky)NC(O), (C1-Csalkyl)C(O)(C1-Csalkyl)N, (Ci-Csalky)C(O)NH, (C1-Caalky)C(O), (C1-Csalkoxy)C(O), HC(O), diphenylmethanimine, C1-Cshaloalkoxy, phenyl, or a 5-membered heteroaromatic ring; or Rsis phenyl substituted with one to three substituents selected from C1-Caalkyl, C1-Cshaloalkyl, Ci- Caalkoxy, Ca-Cecycloalkyl, halogen. CN and hydroxyl: or Rs is a 5-membered heteroaromatic ring substituted with one to three substituents selected from Ci- Caalkyl, Ci-Cahaloalkyl, C1-Caalkoxy, Cs-Cscycloalkyl, halogen, CN and hydroxyl; Rsa and Re are, independently of each other, selected from hydrogen, halogen, CN, C1-Caalkyl, Ci- Cshaloalkyl, Ca-Cacycloalkyl, C1-Caalkoxy, and C1-Cshaloalkoxy: Re is phenyl, benzyl, heteroaryl, or Cs-Cs cycloalkyl; or Res is phenyl, benzyl, heteroaryl, or Cs-Cs cycloalkyl, each of which, independent of each other, is substituted with one to three substituents independently selected from Rx; Rx is independently selected from halogen, Ci-Csalkyl, C1-Cshaloalkyl, C1-Csalkoxy, C1-Cshaloalkoxy, NOz, SFs, CN, C(O)NHz, C(S)NHz, C1-Cshaloalkylsulfanyl, C1-Cshaloalkylsulfinyl, C1- Cshaloalkylsulfonyl, C1-Csalkylsulfanyl, Ci-Caalkylsulfinyl and Ci-Csalkylsulfonyl; Ry is selected from hydrogen, C1-Cs alkyl, C1-Cs haloalkyl, C1-Cs alkoxy, C1-Cs haloalkoxy, halogen, CN and cyclopropyl; and Rz is selected from oxo, halogen, C1-Cs alkyl, C1-Cshaloalkyl, C1-Csalkoxy, C1-Cshaloalkoxy and CN; or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer and N-oxide of the compound of formula I. 2: The compound according to claim 1 wherein Ai and, As are N and Az is CH, and As is CRy and As is CH.

3. The compound according to either claim 1 or claim 2 wherein R' is hydrogen, methyl, ethyl, cyanomethyl, methoxymethyl, cyclopropyl-methyl, allyl, propargyl, benzyloxycarbonyl, or benzyl. 4, The compound according to any one of claims 1 to 3 wherein Rea is halogen, Ci-Cshaloalkyl, C1-Cshaloalkylsulfanyl, C+-Cshaloalkoxy, Cs-Cecycloalkyl, Ca-Cecycloalkyl substituted with one or two substituents independently selected from C1-Cshaloalkyl, cyano, and halogen, Cs-CecycloalkylC1- Caalkyl, Cs-CecycloalkylC1-Csalkyl substituted with one to three substituents independently selected from C1-Cshaloalkyl, cyano, and halogen, Ci-Cscyanoalkyl, C1-Caalkylsulfonyl, C1-Cshaloalkylsulfonyl, C1-Csalkylsulfinyl, C1-Cshaloalkylsulfinyl, Ca-Cecycloalkylsulfanyl, Cs-Cecycloalkylsulfinyl, or Ca- Cecycloalkylsulfonyl.

5. The compound according to any one of claims 1 to 4 wherein Raz is halogen, C1-Cshaloalkyl, C1-Cshaloalkylsulfanyl, Ci-Cahaloalkylsulfonyl, C+-Caalkoxy, Ci-Cahaloalkoxy, or CN.

6. The compound according to any one of claims 1 to 5 wherein Ra is Ci-Caalkyl or Ci- Cshaloalkyl. bo The compound according to any one of claims 1 to 6 wherein Q is Q?, and Rs is pyridine, or pyrimidine; wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from C1-Caalkyl, C1-Cshaloalkyl, C1-Caalkoxy, Ca-Cacycloalkyl, halo, hydroxyl, CN, C-Cshaloalkoxy, Cz-Cshaloalkenyloxy, Cz-Cshaloalkynyloxy, Ca-Cshalocycloalkoxy, and Ca-CecycloalkylCi-Cshaloalkoxy; and Rs is hydrogen, methyl, trifluoromethoxy, methoxy, cyclopropyl, 2,2-difluroroethoxy, 2,2,2-trifluroroethoxy, difluoromethoxy, 2,2,2-trifluroroethyl, chloro, bromo, methoxyethoxy, methylcarbonyl, or methoxycarbonyl.

8. The compound according to any one of claims 1 to 6 wherein Q is Q°, and Rua is pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine, independent of each other, is optionally substituted with one substituent selected from C1-Cshaloalkyl, Cs-Cacycloalkyl, halogen, cyano, Ci-Cshaloakoxy and selected from Y-1 to Y-4; Rsa is hydrogen, halogen, CN, Ci-Csalkyl, C1-Cshaloalkyl, Cs-Cscycloalkyl, C1-Csalkoxy or C1-Cshaloalkoxy; Rss is hydrogen, halogen, CN, Ci-Cshaloalkyl, Cs-Cscycloalkyl, Ci-Csalkoxy, or Ci-Cshaloalkoxy; and Ra, R's and R's independently of each other, are hydrogen, halogen, CN, C1-Csalkyl, Ci-Cshaloalkyl, Cs- Cacycloalkyl, C1-Caalkoxy, and Ci-Cshaloalkoxy.

9. The compound according to claim 1 wherein the formula | is represented by NZ SN Rs NNR T nr J Ry iE Rob. 2 ny Na | 2 9. The compound according Wz ToT R,b SH! Xx a, | ZZ Ry ! Ra Roa (laa) (lab) wherein R1, Rza, Rab, Rs are as defined in any one of claims 1, 3, 4, 5 or 6, and Q: is selected from Q** to Q® and QP to Qf 10 A composition comprising a compound as defined in any one of claims 1 to 9, one or more auxiliaries and diluent, and optionally one or more other active ingredient. 14 A method (i) of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound as defined in any one of claims 1 to 9 or a composition as defined in claim 10; or (ii) for the protection of plant propagation material from the attack by insects, acarines, nematodes or molluscs, which comprises treating the propagation material or the site, where the propagation material is planted, with an effective amount of a compound as defined in any one of claims 1 to 9 or a composition as defined in claim 10; or (iii) of controlling parasites in or on an animal in need thereof comprising administering an effective amount of a compound as defined in any one of claims 1 to 9 or a composition as defined in claim 10.

12. A plant propagation material, such as a seed, comprising, or treated with or adhered thereto, a compound as defined in any one of claims 1 to 9 or a composition as defined in claim 10.

13. A compound of the formula XI(i) R3 A2 At" "AS R3 | RE AA I | I | Ad _A5 R1 Ny ~ N R2a NC XI) wherein Ai, Az, As, As, As, Ri, Rza, Rzp and Rs are as defined in claims 1 to 6.

14. A compound of the formula XIV(i) R3 Gl R1 A2 A SA3 R3 CI | | I R2b SENNA Aq AS RT NA R2a wherein Ai, Az, As, As, As, R1, R2a, R2p and Rs are as defined in claims 1 to 6.

15. A compound of the formula I1(i) A2 AY A3 | R2b. NOS A4___A5 AAS R2a 130) wherein A1, Az, As, As, As, Ree, and Rap are as defined in any one of claims 1, 2, 4 and 5; an a halogen, such as Cl or Br. or a compound of the formula IV(i) A2 AAs R2b NY ONH, A4 __AS > R2a VQ) wherein Ai, Az, As, As, As, Rze, and Rzp are as defined in any one of claims 1, 2, 4 and 5.